chr21-22455091-T-C

Variant names:

• chr21-22455091-T-C
• rs1542876
• ENST00000732680.1:n.258+19570A>G

Variant summary

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

The ENST00000732680.1(ENSG00000295777):​n.258+19570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,632 control chromosomes in the GnomAD database, including 29,403 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 0.62 (29403 hom., cov: 31)
• Consequence: ENSG00000295777 ENST00000732680.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 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+19570A>G		intron_variant	Intron 1 of 1
ENSG00000295777	ENST00000732681.1	n.253+19570A>G		intron_variant	Intron 1 of 2
ENSG00000295777	ENST00000732682.1	n.83-6131A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 93934 AN: 151512 Hom.: 29389 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.620 AC: 93991 AN: 151632 Hom.: 29403 Cov.: 31 AF XY: 0.618 AC XY: 45789 AN XY: 74094

African (AFR) AF: 0.682 AC: 28271 AN: 41424

American (AMR) AF: 0.551 AC: 8376 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2069 AN: 5148

South Asian (SAS) AF: 0.563 AC: 2711 AN: 4814

European-Finnish (FIN) AF: 0.661 AC: 6967 AN: 10534

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 41995 AN: 67730

Other (OTH) AF: 0.582 AC: 1229 AN: 2112

Alfa AF: 0.611 Hom.: 88296

Bravo AF: 0.606

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.020
DANN	Benign	0.46
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs1542876; hg19: chr21-23827411;