rs11200638

chr10-122461028-G-Achr10-122461028-G-T

Variant summary

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

The ENST00000650300.1(ENSG00000285955):n.356C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,162 control chromosomes in the GnomAD database, including 4,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.23 (4399 hom., cov: 34)
• Consequence: ENST00000650300.1 non_coding_transcript_exon
• Clinical Significance: risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: -0.125

Genes affected

(HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105378525	XR_946382.3	n.378C>T		non_coding_transcript_exon_variant	1/3
LOC105378525	XR_946383.3	n.356C>T		non_coding_transcript_exon_variant	1/4
LOC105378525	XR_946384.3	n.356C>T		non_coding_transcript_exon_variant	1/4
LOC105378525	XR_946385.3	n.356C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000650300.1	n.356C>T		non_coding_transcript_exon_variant	1/3
HTRA1	ENST00000648167.1	c.154+2319G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35620 AN: 152042 Hom.: 4389 Cov.: 34

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.234 AC: 35666 AN: 152162 Hom.: 4399 Cov.: 34 AF XY: 0.237 AC XY: 17634 AN XY: 74384

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.235

Alfa AF: 0.213 Hom.: 2603

Bravo AF: 0.236

Asia WGS AF: 0.369 AC: 1277 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Age related macular degeneration 7 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 18, 2015

- -

Susceptibility to neovascular type of age-related macular degeneration Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.4
Dann	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11200638; hg19: chr10-124220544; COSMIC: COSV64564929;