10-122467114-G-T

Variant summary

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

The NM_002775.5(HTRA1):c.472+4990G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,180 control chromosomes in the GnomAD database, including 4,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.23 (4382 hom., cov: 33)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.70

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.472+4990G>T		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.472+4990G>T		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000648167.1	c.154+8405G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35704 AN: 152062 Hom.: 4371 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.235 AC: 35749 AN: 152180 Hom.: 4382 Cov.: 33 AF XY: 0.238 AC XY: 17684 AN XY: 74396

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.237

Alfa AF: 0.208 Hom.: 3371

Bravo AF: 0.238

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.021
Dann	Benign	0.53

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: rs2284665; hg19: chr10-124226630;