rs714816

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002775.5(HTRA1):​c.777+7203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,952 control chromosomes in the GnomAD database, including 7,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7021 hom., cov: 31)

Consequence

HTRA1
NM_002775.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.644
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTRA1NM_002775.5 linkuse as main transcriptc.777+7203G>A intron_variant ENST00000368984.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTRA1ENST00000368984.8 linkuse as main transcriptc.777+7203G>A intron_variant 1 NM_002775.5 P1
HTRA1ENST00000648167.1 linkuse as main transcriptc.459+7203G>A intron_variant

Frequencies

GnomAD3 genomes
AF:
0.284
AC:
43050
AN:
151834
Hom.:
7013
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.128
Gnomad AMI
AF:
0.114
Gnomad AMR
AF:
0.408
Gnomad ASJ
AF:
0.293
Gnomad EAS
AF:
0.380
Gnomad SAS
AF:
0.298
Gnomad FIN
AF:
0.324
Gnomad MID
AF:
0.222
Gnomad NFE
AF:
0.338
Gnomad OTH
AF:
0.288
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.283
AC:
43068
AN:
151952
Hom.:
7021
Cov.:
31
AF XY:
0.285
AC XY:
21168
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.127
Gnomad4 AMR
AF:
0.409
Gnomad4 ASJ
AF:
0.293
Gnomad4 EAS
AF:
0.381
Gnomad4 SAS
AF:
0.298
Gnomad4 FIN
AF:
0.324
Gnomad4 NFE
AF:
0.338
Gnomad4 OTH
AF:
0.287
Alfa
AF:
0.342
Hom.:
15721
Bravo
AF:
0.286
Asia WGS
AF:
0.352
AC:
1219
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
6.3
DANN
Benign
0.43

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.

Other links and lift over

dbSNP: rs714816; hg19: chr10-124256345; API