ENST00000646457.1:n.372-4005T>C

Variant names:

• chr13-76842369-T-C
• rs2876711
• ENST00000646457.1:n.372-4005T>C

Variant summary

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

The ENST00000646457.1(ENSG00000284809):​n.372-4005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,966 control chromosomes in the GnomAD database, including 12,007 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 0.39 (12007 hom., cov: 31)
• Consequence: ENSG00000284809 ENST00000646457.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 11 publications found

Genes affected

ENSG00000284809 (HGNC:58697):

ENSG00000285572 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284809	ENST00000646457.1	n.372-4005T>C		intron_variant	Intron 3 of 3
ENSG00000285572	ENST00000648060.1	n.124+4032A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58847 AN: 151848 Hom.: 12002 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.387 AC: 58875 AN: 151966 Hom.: 12007 Cov.: 31 AF XY: 0.391 AC XY: 29025 AN XY: 74276

African (AFR) AF: 0.317 AC: 13144 AN: 41410

American (AMR) AF: 0.409 AC: 6243 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 923 AN: 3468

East Asian (EAS) AF: 0.749 AC: 3869 AN: 5168

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4814

European-Finnish (FIN) AF: 0.453 AC: 4784 AN: 10552

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27524 AN: 67964

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.393 Hom.: 24178

Bravo AF: 0.385

Asia WGS AF: 0.461 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.81
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs2876711; hg19: chr13-77416504;