chr21-36429136-C-A

Variant names:

• chr21-36429136-C-A
• rs2835345
• ENST00000834987.1:n.124+856G>T

Variant summary

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

The ENST00000834987.1(ENSG00000289221):​n.124+856G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,018 control chromosomes in the GnomAD database, including 4,854 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 0.24 (4854 hom., cov: 32)
• Consequence: ENSG00000289221 ENST00000834987.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 7 publications found

Genes affected

ENSG00000289221 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 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
ENSG00000289221	ENST00000834987.1	n.124+856G>T		intron_variant	Intron 1 of 1
ENSG00000289221	ENST00000691257.1	n.*210G>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35787 AN: 151900 Hom.: 4848 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.236 AC: 35806 AN: 152018 Hom.: 4854 Cov.: 32 AF XY: 0.244 AC XY: 18122 AN XY: 74290

African (AFR) AF: 0.122 AC: 5067 AN: 41492

American (AMR) AF: 0.343 AC: 5243 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2458 AN: 5152

South Asian (SAS) AF: 0.259 AC: 1247 AN: 4808

European-Finnish (FIN) AF: 0.315 AC: 3325 AN: 10546

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16692 AN: 67966

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.251 Hom.: 2119

Bravo AF: 0.235

Asia WGS AF: 0.322 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2835345; hg19: chr21-37801434;