21-43786474-T-C

Variant names:

• chr21-43786474-T-C
• rs1041456

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 0.574 in 151,904 control chromosomes in the GnomAD database, including 27,125 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 0.57 (27125 hom., cov: 31)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 14 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 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: 0.574 AC: 87049 AN: 151784 Hom.: 27074 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.574 AC: 87154 AN: 151904 Hom.: 27125 Cov.: 31 AF XY: 0.580 AC XY: 43093 AN XY: 74248

African (AFR) AF: 0.790 AC: 32745 AN: 41438

American (AMR) AF: 0.635 AC: 9696 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3470

East Asian (EAS) AF: 0.760 AC: 3924 AN: 5160

South Asian (SAS) AF: 0.723 AC: 3484 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4983 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28791 AN: 67902

Other (OTH) AF: 0.560 AC: 1179 AN: 2104

Alfa AF: 0.492 Hom.: 29580

Bravo AF: 0.595

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.77
DANN	Benign	0.18
PhyloP100		-0.59

Splicing

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

Other links and lift over

dbSNP: rs1041456; hg19: chr21-45206355;