21-43348682-C-T

Variant names:

• chr21-43348682-C-T
• rs643608

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 0.683 in 152,060 control chromosomes in the GnomAD database, including 35,778 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 0.68 (35778 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 17 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 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: 0.683 AC: 103775 AN: 151942 Hom.: 35742 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.683 AC: 103862 AN: 152060 Hom.: 35778 Cov.: 32 AF XY: 0.677 AC XY: 50316 AN XY: 74342

African (AFR) AF: 0.752 AC: 31168 AN: 41466

American (AMR) AF: 0.577 AC: 8827 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3468

East Asian (EAS) AF: 0.559 AC: 2884 AN: 5160

South Asian (SAS) AF: 0.568 AC: 2733 AN: 4814

European-Finnish (FIN) AF: 0.662 AC: 7006 AN: 10586

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46546 AN: 67960

Other (OTH) AF: 0.666 AC: 1403 AN: 2108

Alfa AF: 0.680 Hom.: 148505

Bravo AF: 0.682

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.98
DANN	Benign	0.86
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs643608; hg19: chr21-44768562;