rs881666

Variant names:

• chr21-33032958-C-G
• rs881666
• ENST00000454622.2:n.201+37946G>C

Variant summary

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

The ENST00000454622.2(ENSG00000227757):​n.201+37946G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,028 control chromosomes in the GnomAD database, including 8,821 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 0.32 (8821 hom., cov: 32)
• Consequence: ENSG00000227757 ENST00000454622.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817
• Publications: 0 publications found

Genes affected

ENSG00000227757 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 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
ENSG00000227757	ENST00000454622.2	n.201+37946G>C		intron_variant	Intron 1 of 1	2
ENSG00000227757	ENST00000777421.1	n.91+37946G>C		intron_variant	Intron 1 of 1
ENSG00000227757	ENST00000777422.1	n.108-10032G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48421 AN: 151910 Hom.: 8820 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.319 AC: 48440 AN: 152028 Hom.: 8821 Cov.: 32 AF XY: 0.315 AC XY: 23371 AN XY: 74310

African (AFR) AF: 0.196 AC: 8142 AN: 41472

American (AMR) AF: 0.271 AC: 4147 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5180

South Asian (SAS) AF: 0.232 AC: 1120 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4217 AN: 10548

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28334 AN: 67928

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.361 Hom.: 1333

Bravo AF: 0.305

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.47
PhyloP100		-0.82

Splicing

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

Other links and lift over

dbSNP: rs881666; hg19: chr21-34405266;