21-44986375-G-C

Variant names:

• chr21-44986375-G-C
• rs883908

Variant summary

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

The variant allele was found at a frequency of 0.655 in 152,000 control chromosomes in the GnomAD database, including 32,829 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 0.65 (32829 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 3 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 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

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99438 AN: 151882 Hom.: 32795 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.655 AC: 99530 AN: 152000 Hom.: 32829 Cov.: 32 AF XY: 0.653 AC XY: 48523 AN XY: 74278

African (AFR) AF: 0.711 AC: 29457 AN: 41458

American (AMR) AF: 0.603 AC: 9226 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2003 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3719 AN: 5162

South Asian (SAS) AF: 0.768 AC: 3701 AN: 4822

European-Finnish (FIN) AF: 0.636 AC: 6719 AN: 10566

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42585 AN: 67918

Other (OTH) AF: 0.667 AC: 1409 AN: 2112

Alfa AF: 0.530 Hom.: 1491

Bravo AF: 0.650

Asia WGS AF: 0.745 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.53
DANN	Benign	0.63
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs883908; hg19: chr21-46406290; COSMIC: COSV71375273;