rs2823357

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 ENST00000653886.1(ENSG00000229425):​n.331-28652C>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 ENST00000653886.1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000653886.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000229425	ENST00000634644.1	TSL:5	n.355-28652C>T		intron	N/A
	ENSG00000229425	ENST00000634708.1	TSL:5	n.354+32684C>T		intron	N/A
	ENSG00000229425	ENST00000635525.2	TSL:5	n.403-15863C>T		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2823357;

hg19: chr21-16914905;