rs612353

Variant names:

• chr1-34647583-A-G
• rs612353
• ENST00000666642.1:n.569-6569T>C

Variant summary

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

The ENST00000666642.1(ENSG00000287703):​n.569-6569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,104 control chromosomes in the GnomAD database, including 15,466 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 0.45 (15466 hom., cov: 33)
• Consequence: ENSG00000287703 ENST00000666642.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 2 publications found

Genes affected

ENSG00000287703 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105378641	XR_001737964.2	n.156-31888T>C		intron_variant	Intron 1 of 8
LOC105378641	XR_001737965.2	n.156-31888T>C		intron_variant	Intron 1 of 5
LOC105378641	XR_001737966.2	n.156-31888T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287703	ENST00000666642.1	n.569-6569T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67990 AN: 151988 Hom.: 15436 Cov.: 33

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.448 AC: 68078 AN: 152104 Hom.: 15466 Cov.: 33 AF XY: 0.451 AC XY: 33560 AN XY: 74360

African (AFR) AF: 0.494 AC: 20480 AN: 41498

American (AMR) AF: 0.447 AC: 6834 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1737 AN: 5156

South Asian (SAS) AF: 0.509 AC: 2455 AN: 4824

European-Finnish (FIN) AF: 0.494 AC: 5218 AN: 10572

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28323 AN: 67986

Other (OTH) AF: 0.451 AC: 951 AN: 2110

Alfa AF: 0.429 Hom.: 23698

Bravo AF: 0.444

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.59
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs612353; hg19: chr1-35113184; COSMIC: COSV59937584;