10-122481269-C-T

Position:

• chr10-122481269-C-T

Variant summary

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

The NM_002775.5(HTRA1):​c.473-7633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,036 control chromosomes in the GnomAD database, including 3,225 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 0.19 (3225 hom., cov: 32)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.473-7633C>T		intron_variant		ENST00000368984.8	NP_002766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTRA1	ENST00000368984.8	c.473-7633C>T		intron_variant		1	NM_002775.5	ENSP00000357980.3
HTRA1	ENST00000648167.1	c.155-7633C>T		intron_variant				ENSP00000498033.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29556 AN: 151918 Hom.: 3220 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.195 AC: 29593 AN: 152036 Hom.: 3225 Cov.: 32 AF XY: 0.200 AC XY: 14839 AN XY: 74294

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.207

Alfa AF: 0.184 Hom.: 1511

Bravo AF: 0.192

Asia WGS AF: 0.353 AC: 1231 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	0.21
DANN	Benign	0.40

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: rs2284666; hg19: chr10-124240785;