21-46597307-G-A

Variant names:

• chr21-46597307-G-A
• rs2839350
• ENST00000794725.1:n.171-475C>T

Variant summary

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

The ENST00000794725.1(ENSG00000303462):​n.171-475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,140 control chromosomes in the GnomAD database, including 3,788 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 0.21 (3788 hom., cov: 32)
• Consequence: ENSG00000303462 ENST00000794725.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 10 publications found

Genes affected

ENSG00000303462 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 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
ENSG00000303462	ENST00000794725.1	n.171-475C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32495 AN: 152022 Hom.: 3774 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.214 AC: 32537 AN: 152140 Hom.: 3788 Cov.: 32 AF XY: 0.213 AC XY: 15823 AN XY: 74386

African (AFR) AF: 0.300 AC: 12432 AN: 41486

American (AMR) AF: 0.142 AC: 2176 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3464

East Asian (EAS) AF: 0.0188 AC: 97 AN: 5168

South Asian (SAS) AF: 0.174 AC: 842 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2507 AN: 10586

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13187 AN: 67994

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.197 Hom.: 4209

Bravo AF: 0.207

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.26
PhyloP100		0.056

Splicing

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

Other links and lift over

dbSNP: rs2839350; hg19: chr21-48017220;