10-122460545-A-G

Position:

• chr10-122460545-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000285955 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105378525	XR_946382.3	n.457+404T>C		intron_variant
LOC105378525	XR_946383.3	n.435+404T>C		intron_variant
LOC105378525	XR_946384.3	n.435+404T>C		intron_variant
LOC105378525	XR_946385.3	n.435+404T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000648167.1	c.154+1836A>G		intron_variant				ENSP00000498033.1
ENSG00000285955	ENST00000650300.1	n.435+404T>C		intron_variant

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

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.235

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3763764; hg19: chr10-124220061;