21-33067583-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

ENSG00000227757 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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

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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.755

Alfa AF: 0.717 Hom.: 54827

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs928736; hg19: chr21-34439889;