rs2293870

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002775.5(HTRA1):c.108G>C(p.Gly36Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,101,636 control chromosomes in the GnomAD database, including 10,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G36G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 1146 hom., cov: 32)

Exomes 𝑓: 0.14 ( 9517 hom. )

Consequence

HTRA1
NM_002775.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -1.25

Publications

32 publications found

Variant links:

Genes affected

HTRA1 (HGNC:9476): (HtrA serine peptidase 1) This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]

HTRA1 Gene-Disease associations (from GenCC):

CARASIL syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
genetic cerebral small vessel disease
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
HTRA1-related autosomal dominant cerebral small vessel disease
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

HTRA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-122461760-G-C is Benign according to our data. Variant chr10-122461760-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 21325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1	NM_002775.5 link	c.108G>C	p.Gly36Gly	synonymous_variant	Exon 1 of 9	ENST00000368984.8	NP_002766.1	Q92743

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8 link	c.108G>C	p.Gly36Gly	synonymous_variant	Exon 1 of 9	1	NM_002775.5	ENSP00000357980.3		Q92743
HTRA1	ENST00000648167.1 link	c.154+3051G>C		intron_variant	Intron 1 of 8			ENSP00000498033.1		A0A3B3IU24

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15298

AN:

147106

Hom.:

1146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.000594

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0545

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.0595

AC:

1060

AN:

17818

AF XY:

0.0579

show subpopulations

Gnomad AFR exome

AF:

0.0245

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0706

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0918

Gnomad NFE exome

AF:

0.0895

Gnomad OTH exome

AF:

0.0761

GnomAD4 exome

AF:

0.136

AC:

130142

AN:

954426

Hom.:

9517

Cov.:

AF XY:

0.135

AC XY:

61811

AN XY:

457794

show subpopulations

African (AFR)

AF:

0.0129

AC:

232

AN:

18008

American (AMR)

AF:

0.0578

AC:

396

AN:

6850

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

972

AN:

8698

East Asian (EAS)

AF:

0.0000955

AC:

AN:

10468

South Asian (SAS)

AF:

0.0305

AC:

869

AN:

28508

European-Finnish (FIN)

AF:

0.122

AC:

1136

AN:

9280

Middle Eastern (MID)

AF:

0.0545

AC:

117

AN:

2148

European-Non Finnish (NFE)

AF:

0.147

AC:

122713

AN:

837078

Other (OTH)

AF:

0.111

AC:

3706

AN:

33388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5778

11556

17333

23111

28889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5454

10908

16362

21816

27270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.104

AC:

15294

AN:

147210

Hom.:

1146

Cov.:

AF XY:

0.102

AC XY:

7301

AN XY:

71650

show subpopulations

African (AFR)

AF:

0.0261

AC:

1072

AN:

41000

American (AMR)

AF:

0.107

AC:

1582

AN:

14840

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

456

AN:

3392

East Asian (EAS)

AF:

0.000596

AC:

AN:

5036

South Asian (SAS)

AF:

0.0295

AC:

142

AN:

4820

European-Finnish (FIN)

AF:

0.164

AC:

1442

AN:

8768

Middle Eastern (MID)

AF:

0.0552

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.155

AC:

10243

AN:

66110

Other (OTH)

AF:

0.111

AC:

227

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

676

1351

2027

2702

3378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0838

Hom.:

195

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26310622, 18164066, 23478260) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Macular degeneration

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CARASIL syndrome

Benign:1Other:1

Jun 01, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

not specified

Benign:1

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

-1.2

PromoterAI

0.049

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over