chr21-26871278-A-G

Variant names:

• chr21-26871278-A-G
• rs229116
• ENST00000837716.1:n.490+1082T>C

Variant summary

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

The ENST00000837716.1(ENSG00000309000):​n.490+1082T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,128 control chromosomes in the GnomAD database, including 19,648 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 0.50 (19648 hom., cov: 33)
• Consequence: ENSG00000309000 ENST00000837716.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 4 publications found

Genes affected

ENSG00000309000 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000837716.1. 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
	ENSG00000309000	ENST00000837716.1		n.490+1082T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75867 AN: 152010 Hom.: 19620 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.499 AC: 75948 AN: 152128 Hom.: 19648 Cov.: 33 AF XY: 0.493 AC XY: 36654 AN XY: 74366

African (AFR) AF: 0.638 AC: 26453 AN: 41494

American (AMR) AF: 0.505 AC: 7723 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1777 AN: 5166

South Asian (SAS) AF: 0.488 AC: 2353 AN: 4826

European-Finnish (FIN) AF: 0.336 AC: 3553 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30928 AN: 67994

Other (OTH) AF: 0.464 AC: 982 AN: 2116

Alfa AF: 0.462 Hom.: 2287

Bravo AF: 0.515

Asia WGS AF: 0.456 AC: 1586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.54
PhyloP100		0.35

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: rs229116;

hg19: chr21-28243597;

COSMIC: COSV53892031;