21-33067583-C-T

Variant names:

• chr21-33067583-C-T
• rs928736
• ENST00000454622.2:n.201+3321G>A

Variant summary

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

The ENST00000454622.2(ENSG00000227757):​n.201+3321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,218 control chromosomes in the GnomAD database, including 42,777 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 0.75 (42777 hom., cov: 33)
• Consequence: ENSG00000227757 ENST00000454622.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 28 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 (SAS) allele frequency at 95% confidence interval = 0.818 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+3321G>A		intron_variant	Intron 1 of 1	2
ENSG00000227757	ENST00000777421.1	n.91+3321G>A		intron_variant	Intron 1 of 1
ENSG00000227757	ENST00000777422.1	n.107+3321G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113575 AN: 152100 Hom.: 42722 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.747 AC: 113687 AN: 152218 Hom.: 42777 Cov.: 33 AF XY: 0.750 AC XY: 55822 AN XY: 74408

African (AFR) AF: 0.820 AC: 34075 AN: 41548

American (AMR) AF: 0.727 AC: 11126 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2483 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4170 AN: 5170

South Asian (SAS) AF: 0.840 AC: 4052 AN: 4826

European-Finnish (FIN) AF: 0.703 AC: 7440 AN: 10578

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47873 AN: 68000

Other (OTH) AF: 0.755 AC: 1595 AN: 2112

Alfa AF: 0.718 Hom.: 76456

Bravo AF: 0.746

Asia WGS AF: 0.821 AC: 2854 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	0.29
DANN	Benign	0.49
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs928736; hg19: chr21-34439889;