rs2672585

Positions:

• chr10-122508885-C-G

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.1120+115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 717,230 control chromosomes in the GnomAD database, including 40,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7325 hom., cov: 32)
  • Exomes 𝑓: 0.33 (32780 hom.)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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=-0.9).
• BP6: Variant 10-122508885-C-G is Benign according to our data. Variant chr10-122508885-C-G is described in ClinVar as [Benign]. Clinvar id is 1246855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.1120+115C>G		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.1120+115C>G		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000420892.1	c.343+115C>G		intron_variant		2
HTRA1	ENST00000648167.1	c.802+115C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45085 AN: 151956 Hom.: 7310 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.333 AC: 188081 AN: 565154 Hom.: 32780 AF XY: 0.328 AC XY: 100053 AN XY: 305416

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.297 AC: 45126 AN: 152076 Hom.: 7325 Cov.: 32 AF XY: 0.299 AC XY: 22197 AN XY: 74324

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.300

Alfa AF: 0.318 Hom.: 995

Bravo AF: 0.303

Asia WGS AF: 0.359 AC: 1244 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.41

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: rs2672585; hg19: chr10-124268401; COSMIC: COSV64565073;