chr21-30453446-C-T

Variant names:

• chr21-30453446-C-T
• rs2832886
• ENST00000730239.1:n.198-7717G>A

Variant summary

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

The ENST00000730239.1(ENSG00000295465):​n.198-7717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,974 control chromosomes in the GnomAD database, including 26,647 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 0.59 (26647 hom., cov: 32)
• Consequence: ENSG00000295465 ENST00000730239.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 2 publications found

Genes affected

ENSG00000295465 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372772	XR_937653.3	n.195+19918G>A		intron_variant	Intron 3 of 3
LOC105372772	XR_937654.3	n.101-7717G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295465	ENST00000730239.1	n.198-7717G>A		intron_variant	Intron 2 of 3
ENSG00000295465	ENST00000730240.1	n.104-7717G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89244 AN: 151858 Hom.: 26618 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.588 AC: 89324 AN: 151974 Hom.: 26647 Cov.: 32 AF XY: 0.585 AC XY: 43418 AN XY: 74272

African (AFR) AF: 0.642 AC: 26586 AN: 41440

American (AMR) AF: 0.622 AC: 9500 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3468

East Asian (EAS) AF: 0.296 AC: 1528 AN: 5156

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4824

European-Finnish (FIN) AF: 0.509 AC: 5377 AN: 10560

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39298 AN: 67942

Other (OTH) AF: 0.593 AC: 1251 AN: 2110

Alfa AF: 0.594 Hom.: 3505

Bravo AF: 0.596

Asia WGS AF: 0.494 AC: 1721 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	0.81
DANN	Benign	0.62
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs2832886; hg19: chr21-31825764;