Variant 10-122461596-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002775.5(HTRA1):c.-57C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,134,978 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 20 hom., cov: 32)

Exomes 𝑓: 0.017 ( 186 hom. )

Consequence

HTRA1
NM_002775.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.03

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-122461596-C-A is Benign according to our data. Variant chr10-122461596-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 299042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2041/148090) while in subpopulation NFE AF= 0.0169 (1123/66366). AF 95% confidence interval is 0.0161. There are 20 homozygotes in gnomad4. There are 951 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5 linkuse as main transcript	c.-57C>A		5_prime_UTR_variant	1/9	ENST00000368984.8	NP_002766.1	Q92743

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984 linkuse as main transcript	c.-57C>A		5_prime_UTR_variant	1/9	1	NM_002775.5	ENSP00000357980.3		Q92743
HTRA1	ENST00000648167.1 linkuse as main transcript	c.154+2887C>A		intron_variant				ENSP00000498033.1		A0A3B3IU24

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2041

AN:

147978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00737

Gnomad MID

AF:

0.0160

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0147

GnomAD3 exomes

AF:

0.0145

AC:

998

AN:

68984

Hom.:

AF XY:

0.0149

AC XY:

596

AN XY:

40040

show subpopulations

Gnomad AFR exome

AF:

0.00882

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.0344

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.00727

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0168

AC:

16540

AN:

986888

Hom.:

186

Cov.:

AF XY:

0.0168

AC XY:

8294

AN XY:

493270

show subpopulations

Gnomad4 AFR exome

AF:

0.00877

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.0354

Gnomad4 EAS exome

AF:

0.0000780

Gnomad4 SAS exome

AF:

0.0137

Gnomad4 FIN exome

AF:

0.00831

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0173

GnomAD4 genome

AF:

0.0138

AC:

2041

AN:

148090

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

951

AN XY:

72120

show subpopulations

Gnomad4 AFR

AF:

0.00938

Gnomad4 AMR

AF:

0.0168

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.0125

Gnomad4 FIN

AF:

0.00737

Gnomad4 NFE

AF:

0.0169

Gnomad4 OTH

AF:

0.0146

Alfa

AF:

0.0165

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.89

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