Variant rs1049331 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002775.5(HTRA1):c.102C>T(p.Ala34Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,116,160 control chromosomes in the GnomAD database, including 30,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4227 hom., cov: 32)

Exomes 𝑓: 0.23 ( 25989 hom. )

Consequence

HTRA1
NM_002775.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.152

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 10-122461754-C-T is Benign according to our data. Variant chr10-122461754-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 21324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-122461754-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.152 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5 linkuse as main transcript	c.102C>T	p.Ala34Ala	synonymous_variant	1/9	ENST00000368984.8	NP_002766.1	Q92743

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8 linkuse as main transcript	c.102C>T	p.Ala34Ala	synonymous_variant	1/9	1	NM_002775.5	ENSP00000357980.3		Q92743
HTRA1	ENST00000648167.1 linkuse as main transcript	c.154+3045C>T		intron_variant				ENSP00000498033.1		A0A3B3IU24

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

34440

AN:

147136

Hom.:

4216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.235

GnomAD3 exomes

AF:

0.323

AC:

6476

AN:

20024

Hom.:

1072

AF XY:

0.328

AC XY:

4068

AN XY:

12400

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.522

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.226

AC:

219284

AN:

968916

Hom.:

25989

Cov.:

AF XY:

0.228

AC XY:

106332

AN XY:

466516

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.291

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.234

AC:

34488

AN:

147244

Hom.:

4227

Cov.:

AF XY:

0.237

AC XY:

16979

AN XY:

71708

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.246

Hom.:

566

Asia WGS

AF:

0.340

AC:

957

AN:

2826

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 23478260, 18164066, 26310622) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Macular degeneration

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

CARASIL syndrome

Benign:1Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 01, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.5

DANN

Benign

0.96

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