ENST00000648167.1:c.154+1836A>G

Variant names:

• chr10-122460545-A-G
• rs3763764
• ENST00000648167.1:c.154+1836A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648167.1(HTRA1):​c.154+1836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,884 control chromosomes in the GnomAD database, including 4,473 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 0.24 (4473 hom., cov: 32)
• Consequence: HTRA1 ENST00000648167.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352
• Publications: 7 publications found

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

ENSG00000285955 (HGNC:58122):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648167.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTRA1	ENST00000648167.1		c.154+1836A>G		intron	N/A	ENSP00000498033.1
	ENSG00000285955	ENST00000650300.1		n.435+404T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35922 AN: 151764 Hom.: 4464 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.237 AC: 35970 AN: 151884 Hom.: 4473 Cov.: 32 AF XY: 0.240 AC XY: 17792 AN XY: 74250

African (AFR) AF: 0.243 AC: 10053 AN: 41442

American (AMR) AF: 0.230 AC: 3519 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2170 AN: 5098

South Asian (SAS) AF: 0.318 AC: 1525 AN: 4802

European-Finnish (FIN) AF: 0.234 AC: 2480 AN: 10578

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14730 AN: 67910

Other (OTH) AF: 0.235 AC: 495 AN: 2108

Alfa AF: 0.247 Hom.: 588

Bravo AF: 0.239

Asia WGS AF: 0.371 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.8
DANN	Benign	0.46
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs3763764; hg19: chr10-124220061;