rs2823256

Variant names:

• chr21-15412387-G-A
• rs2823256
• ENST00000634642.1:n.344-11838C>T

Variant summary

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

The ENST00000634642.1(ENSG00000229425):​n.344-11838C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,792 control chromosomes in the GnomAD database, including 5,329 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 0.26 (5329 hom., cov: 31)
• Consequence: ENSG00000229425 ENST00000634642.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927745	NR_188234.1	n.342-11838C>T		intron_variant	Intron 2 of 8
LOC101927745	NR_188235.1	n.342-11838C>T		intron_variant	Intron 2 of 6
LOC101927745	NR_188236.1	n.342-11838C>T		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000229425	ENST00000634642.1	n.344-11838C>T		intron_variant	Intron 1 of 6	3
ENSG00000229425	ENST00000634644.1	n.953-16890C>T		intron_variant	Intron 8 of 11	5
ENSG00000229425	ENST00000634708.1	n.424-11838C>T		intron_variant	Intron 3 of 9	5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39601 AN: 151676 Hom.: 5311 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.261 AC: 39654 AN: 151792 Hom.: 5329 Cov.: 31 AF XY: 0.256 AC XY: 18994 AN XY: 74132

African (AFR) AF: 0.215 AC: 8888 AN: 41394

American (AMR) AF: 0.246 AC: 3740 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1573 AN: 5150

South Asian (SAS) AF: 0.231 AC: 1109 AN: 4802

European-Finnish (FIN) AF: 0.220 AC: 2320 AN: 10528

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20233 AN: 67924

Other (OTH) AF: 0.268 AC: 565 AN: 2108

Alfa AF: 0.286 Hom.: 10569

Bravo AF: 0.264

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs2823256; hg19: chr21-16784706;