rs714816

Positions:

• chr10-122496829-G-A

Variant summary

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

The NM_002775.5(HTRA1):​c.777+7203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,952 control chromosomes in the GnomAD database, including 7,021 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 (7021 hom., cov: 31)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.777+7203G>A		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.777+7203G>A		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000648167.1	c.459+7203G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43050 AN: 151834 Hom.: 7013 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.283 AC: 43068 AN: 151952 Hom.: 7021 Cov.: 31 AF XY: 0.285 AC XY: 21168 AN XY: 74264

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.287

Alfa AF: 0.342 Hom.: 15721

Bravo AF: 0.286

Asia WGS AF: 0.352 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.43

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: rs714816; hg19: chr10-124256345;