10-122464428-C-T

Position:

• chr10-122464428-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.472+2304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,914 control chromosomes in the GnomAD database, including 20,513 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 0.52 (20513 hom., cov: 31)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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 (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTRA1	NM_002775.5	c.472+2304C>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.472+2304C>T		intron_variant		1	NM_002775.5	ENSP00000357980	P1
HTRA1	ENST00000648167.1	c.154+5719C>T		intron_variant				ENSP00000498033

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78175 AN: 151796 Hom.: 20486 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.515 AC: 78259 AN: 151914 Hom.: 20513 Cov.: 31 AF XY: 0.514 AC XY: 38153 AN XY: 74232

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.500

Alfa AF: 0.501 Hom.: 34750

Bravo AF: 0.518

Asia WGS AF: 0.607 AC: 2109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.35

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: rs2248799; hg19: chr10-124223944;