21-38684499-A-C

Variant names:

• chr21-38684499-A-C
• rs743446

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 0.493 in 152,010 control chromosomes in the GnomAD database, including 18,425 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 0.49 (18425 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 14 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.518 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: 0.493 AC: 74845 AN: 151890 Hom.: 18417 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.493 AC: 74880 AN: 152010 Hom.: 18425 Cov.: 32 AF XY: 0.489 AC XY: 36360 AN XY: 74300

African (AFR) AF: 0.463 AC: 19181 AN: 41450

American (AMR) AF: 0.528 AC: 8066 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1728 AN: 3466

East Asian (EAS) AF: 0.490 AC: 2525 AN: 5152

South Asian (SAS) AF: 0.465 AC: 2238 AN: 4818

European-Finnish (FIN) AF: 0.488 AC: 5153 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34413 AN: 67956

Other (OTH) AF: 0.468 AC: 990 AN: 2116

Alfa AF: 0.503 Hom.: 70796

Bravo AF: 0.496

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs743446; hg19: chr21-40056423;