dbSNP rs2672585: HTRA1:c.1120+115C>G (chr10-122508885-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002775.5(HTRA1):c.1120+115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 717,230 control chromosomes in the GnomAD database, including 40,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7325 hom., cov: 32)

Exomes 𝑓: 0.33 ( 32780 hom. )

Consequence

HTRA1
NM_002775.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-122508885-C-G is Benign according to our data. Variant chr10-122508885-C-G is described in ClinVar as [Benign]. Clinvar id is 1246855.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1	NM_002775.5 link	c.1120+115C>G		intron_variant	Intron 6 of 8	ENST00000368984.8	NP_002766.1	Q92743

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTRA1	ENST00000368984.8 link	c.1120+115C>G	intron_variant	Intron 6 of 8	1	NM_002775.5	ENSP00000357980.3	Q92743
HTRA1	ENST00000648167.1 link	c.802+115C>G	intron_variant	Intron 6 of 8			ENSP00000498033.1	A0A3B3IU24
HTRA1	ENST00000420892.1 link	c.343+115C>G	intron_variant	Intron 3 of 5	2		ENSP00000412676.1	H0Y7G9

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45085

AN:

151956

Hom.:

7310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.302

GnomAD4 exome

AF:

0.333

AC:

188081

AN:

565154

Hom.:

32780

AF XY:

0.328

AC XY:

100053

AN XY:

305416

show subpopulations

Gnomad4 AFR exome

AF:

0.184

AC:

2931

AN:

15956

Gnomad4 AMR exome

AF:

0.521

AC:

18461

AN:

35436

Gnomad4 ASJ exome

AF:

0.303

AC:

5954

AN:

19682

Gnomad4 EAS exome

AF:

0.378

AC:

12710

AN:

33586

Gnomad4 SAS exome

AF:

0.299

AC:

19408

AN:

64962

Gnomad4 FIN exome

AF:

0.320

AC:

12710

AN:

39746

Gnomad4 NFE exome

AF:

0.327

AC:

105547

AN:

322634

Gnomad4 Remaining exome

AF:

0.319

AC:

9738

AN:

30496

Heterozygous variant carriers

6604

13207

19811

26414

33018

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.297

AC:

45126

AN:

152076

Hom.:

7325

Cov.:

AF XY:

0.299

AC XY:

22197

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.188

AC:

0.187964

AN:

0.187964

Gnomad4 AMR

AF:

0.418

AC:

0.417506

AN:

0.417506

Gnomad4 ASJ

AF:

0.295

AC:

0.294524

AN:

0.294524

Gnomad4 EAS

AF:

0.385

AC:

0.384511

AN:

0.384511

Gnomad4 SAS

AF:

0.299

AC:

0.299085

AN:

0.299085

Gnomad4 FIN

AF:

0.322

AC:

0.321625

AN:

0.321625

Gnomad4 NFE

AF:

0.328

AC:

0.328205

AN:

0.328205

Gnomad4 OTH

AF:

0.300

AC:

0.29981

AN:

0.29981

Heterozygous variant carriers

1589

3178

4766

6355

7944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.318

Hom.:

995

Bravo

AF:

0.303

Asia WGS

AF:

0.359

AC:

1244

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.055

DANN

Benign

0.41

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over