chr21-22453132-C-T

Variant names:

• chr21-22453132-C-T
• rs1041778
• ENST00000732680.1:n.258+21529G>A

Variant summary

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

The ENST00000732680.1(ENSG00000295777):​n.258+21529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,526 control chromosomes in the GnomAD database, including 25,477 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 0.58 (25477 hom., cov: 32)
• Consequence: ENSG00000295777 ENST00000732680.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 3 publications found

Genes affected

ENSG00000295777 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 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
ENSG00000295777	ENST00000732680.1	n.258+21529G>A		intron_variant	Intron 1 of 1
ENSG00000295777	ENST00000732681.1	n.253+21529G>A		intron_variant	Intron 1 of 2
ENSG00000295777	ENST00000732682.1	n.83-4172G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87465 AN: 151408 Hom.: 25464 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.578 AC: 87514 AN: 151526 Hom.: 25477 Cov.: 32 AF XY: 0.577 AC XY: 42690 AN XY: 74024

African (AFR) AF: 0.534 AC: 22088 AN: 41330

American (AMR) AF: 0.532 AC: 8106 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3466

East Asian (EAS) AF: 0.411 AC: 2115 AN: 5142

South Asian (SAS) AF: 0.562 AC: 2709 AN: 4822

European-Finnish (FIN) AF: 0.672 AC: 7050 AN: 10488

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.619 AC: 41919 AN: 67748

Other (OTH) AF: 0.555 AC: 1167 AN: 2102

Alfa AF: 0.591 Hom.: 42728

Bravo AF: 0.559

Asia WGS AF: 0.508 AC: 1765 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.71
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1041778; hg19: chr21-23825452;