rs2239587

chr10-122489793-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002775.5(HTRA1):c.777+167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,934 control chromosomes in the GnomAD database, including 1,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1955 hom., cov: 32)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-122489793-G-A is Benign according to our data. Variant chr10-122489793-G-A is described in ClinVar as [Benign]. Clinvar id is 1245621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.777+167G>A		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.777+167G>A		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000648167.1	c.459+167G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22401 AN: 151816 Hom.: 1948 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.148 AC: 22445 AN: 151934 Hom.: 1955 Cov.: 32 AF XY: 0.152 AC XY: 11316 AN XY: 74270

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.160

Alfa AF: 0.128 Hom.: 155

Bravo AF: 0.153

Asia WGS AF: 0.320 AC: 1116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.3
Dann	Benign	0.61

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: rs2239587; hg19: chr10-124249309; COSMIC: COSV64565254;