chr21-28510020-C-T

Variant names:

• chr21-28510020-C-T
• rs2205374
• ENST00000430247.1:n.127-26951G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000433310.6(ENSG00000232855):​n.457-63548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,072 control chromosomes in the GnomAD database, including 32,968 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 0.65 (32968 hom., cov: 32)
• Consequence: ENSG00000232855 ENST00000433310.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

ENSG00000232855 (HGNC:58104):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 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
ENSG00000232855	ENST00000430247.1	n.127-26951G>A		intron_variant	Intron 2 of 4	5
ENSG00000232855	ENST00000433310.6	n.457-63548G>A		intron_variant	Intron 3 of 4	2
ENSG00000232855	ENST00000659279.1	n.229-26951G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98399 AN: 151954 Hom.: 32966 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.647 AC: 98428 AN: 152072 Hom.: 32968 Cov.: 32 AF XY: 0.644 AC XY: 47851 AN XY: 74354

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.648

Alfa AF: 0.691 Hom.: 4578

Bravo AF: 0.625

Asia WGS AF: 0.376 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.99
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2205374; hg19: chr21-29882341;