21-28510020-C-T

Variant names:

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

Variant summary

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

The ENST00000430247.1(ENSG00000232855):​n.127-26951G>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 ENST00000430247.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 publications found

Genes affected

ENSG00000232855 (HGNC:58104):

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.574 AC: 23804 AN: 41460

American (AMR) AF: 0.553 AC: 8447 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1009 AN: 5172

South Asian (SAS) AF: 0.583 AC: 2810 AN: 4822

European-Finnish (FIN) AF: 0.792 AC: 8381 AN: 10580

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49476 AN: 67972

Other (OTH) AF: 0.648 AC: 1365 AN: 2108

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
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2205374; hg19: chr21-29882341;