10-122505362-T-C

Position:

• chr10-122505362-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002775.5(HTRA1):​c.778-1329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,112 control chromosomes in the GnomAD database, including 6,858 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 (6858 hom., cov: 32)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.778-1329T>C		intron_variant		ENST00000368984.8	NP_002766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8	c.778-1329T>C		intron_variant		1	NM_002775.5	ENSP00000357980.3
HTRA1	ENST00000648167.1	c.460-1329T>C		intron_variant				ENSP00000498033.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42698 AN: 151994 Hom.: 6848 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.281 AC: 42722 AN: 152112 Hom.: 6858 Cov.: 32 AF XY: 0.283 AC XY: 21045 AN XY: 74344

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.282

Alfa AF: 0.321 Hom.: 1456

Bravo AF: 0.284

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2250804; hg19: chr10-124264878;