ENST00000647969.1:n.183-587T>C

Variant names:

• chr10-122451496-A-G
• rs2736930
• ENST00000647969.1:n.183-587T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647969.1(ENSG00000285955):​n.183-587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,166 control chromosomes in the GnomAD database, including 1,404 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 0.12 (1404 hom., cov: 32)
• Consequence: ENSG00000285955 ENST00000647969.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 4 publications found

Genes affected

ENSG00000285955 (HGNC:58122):

ENSG00000305527 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTRA1-AS1	XR_946382.3	n.1875-557T>C		intron_variant	Intron 2 of 2
HTRA1-AS1	XR_946383.3	n.1853-557T>C		intron_variant	Intron 2 of 3
HTRA1-AS1	XR_946384.3	n.1602-557T>C		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285955	ENST00000647969.1	n.183-587T>C		intron_variant	Intron 1 of 1
ENSG00000285955	ENST00000650300.1	n.1852+6999T>C		intron_variant	Intron 2 of 2
ENSG00000285955	ENST00000811415.1	n.374-839T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17514 AN: 151052 Hom.: 1403 Cov.: 32

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.000613

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.116 AC: 17514 AN: 151166 Hom.: 1404 Cov.: 32 AF XY: 0.113 AC XY: 8342 AN XY: 73806

African (AFR) AF: 0.0298 AC: 1237 AN: 41518

American (AMR) AF: 0.123 AC: 1819 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3462

East Asian (EAS) AF: 0.000615 AC: 3 AN: 4882

South Asian (SAS) AF: 0.0338 AC: 162 AN: 4788

European-Finnish (FIN) AF: 0.166 AC: 1747 AN: 10536

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11644 AN: 67926

Other (OTH) AF: 0.129 AC: 271 AN: 2102

Alfa AF: 0.136 Hom.: 222

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs2736930; hg19: chr10-124211012;