rs2672588

Positions:

• chr10-122475780-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.473-13122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,190 control chromosomes in the GnomAD database, including 5,848 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 0.27 (5848 hom., cov: 34)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.473-13122T>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.473-13122T>C		intron_variant		1	NM_002775.5	ENSP00000357980	P1
HTRA1	ENST00000648167.1	c.155-13122T>C		intron_variant				ENSP00000498033

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40922 AN: 152072 Hom.: 5850 Cov.: 34

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.269 AC: 40940 AN: 152190 Hom.: 5848 Cov.: 34 AF XY: 0.262 AC XY: 19526 AN XY: 74424

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0771

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.268

Alfa AF: 0.257 Hom.: 9460

Bravo AF: 0.272

Asia WGS AF: 0.0980 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Benign	0.74

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: rs2672588; hg19: chr10-124235296;