rs7093894

chr10-122475364-C-A

Variant summary

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

The NM_002775.5(HTRA1):c.472+13240C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,190 control chromosomes in the GnomAD database, including 4,548 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 0.22 (4548 hom., cov: 33)
• Consequence: HTRA1 NM_002775.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTRA1	NM_002775.5	c.472+13240C>A		intron_variant		ENST00000368984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTRA1	ENST00000368984.8	c.472+13240C>A		intron_variant		1	NM_002775.5	P1
HTRA1	ENST00000648167.1	c.155-13538C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33126 AN: 152070 Hom.: 4548 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.218 AC: 33149 AN: 152190 Hom.: 4548 Cov.: 33 AF XY: 0.215 AC XY: 16032 AN XY: 74408

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.0872

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.215

Alfa AF: 0.163 Hom.: 2319

Bravo AF: 0.227

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	15
Dann	Benign	0.65

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: rs7093894; hg19: chr10-124234880;