chr21-15542586-G-A

Variant names:

• chr21-15542586-G-A
• rs2823357
• ENST00000634644.1:n.355-28652C>T

Variant summary

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

The ENST00000634644.1(ENSG00000229425):​n.355-28652C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,014 control chromosomes in the GnomAD database, including 18,739 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 0.47 (18739 hom., cov: 32)
• Consequence: ENSG00000229425 ENST00000634644.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 24 publications found

Genes affected

ENSG00000229425 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369302	XR_001754972.2	n.357-15863C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000229425	ENST00000634644.1	n.355-28652C>T		intron_variant	Intron 2 of 11	5
ENSG00000229425	ENST00000634708.1	n.354+32684C>T		intron_variant	Intron 2 of 9	5
ENSG00000229425	ENST00000635525.2	n.403-15863C>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72038 AN: 151894 Hom.: 18705 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.474 AC: 72113 AN: 152014 Hom.: 18739 Cov.: 32 AF XY: 0.473 AC XY: 35120 AN XY: 74286

African (AFR) AF: 0.708 AC: 29383 AN: 41478

American (AMR) AF: 0.449 AC: 6847 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1391 AN: 3462

East Asian (EAS) AF: 0.325 AC: 1679 AN: 5168

South Asian (SAS) AF: 0.433 AC: 2083 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3963 AN: 10542

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25310 AN: 67980

Other (OTH) AF: 0.488 AC: 1029 AN: 2108

Alfa AF: 0.405 Hom.: 44606

Bravo AF: 0.488

Asia WGS AF: 0.393 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.027

Splicing

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

Other links and lift over

dbSNP: rs2823357; hg19: chr21-16914905;