21-25272769-C-T

Variant names:

• chr21-25272769-C-T
• rs9977253
• ENST00000409758.1:n.89+60968G>A

Variant summary

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

The ENST00000409758.1(ENSG00000222042):​n.89+60968G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 151,632 control chromosomes in the GnomAD database, including 45,859 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 0.77 (45859 hom., cov: 31)
• Consequence: ENSG00000222042 ENST00000409758.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 10 publications found

Genes affected

ENSG00000222042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 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
ENSG00000222042	ENST00000409758.1	n.89+60968G>A		intron_variant	Intron 1 of 3	3
ENSG00000222042	ENST00000656005.1	n.217+88419G>A		intron_variant	Intron 2 of 4
ENSG00000222042	ENST00000667825.2	n.313+88419G>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116363 AN: 151514 Hom.: 45798 Cov.: 31

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.768 AC: 116484 AN: 151632 Hom.: 45859 Cov.: 31 AF XY: 0.770 AC XY: 57077 AN XY: 74108

African (AFR) AF: 0.937 AC: 38861 AN: 41484

American (AMR) AF: 0.773 AC: 11730 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2230 AN: 3460

East Asian (EAS) AF: 0.929 AC: 4802 AN: 5168

South Asian (SAS) AF: 0.788 AC: 3802 AN: 4822

European-Finnish (FIN) AF: 0.718 AC: 7590 AN: 10564

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45151 AN: 67644

Other (OTH) AF: 0.725 AC: 1529 AN: 2110

Alfa AF: 0.702 Hom.: 139407

Bravo AF: 0.782

Asia WGS AF: 0.892 AC: 3102 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	0.17
DANN	Benign	0.45
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs9977253; hg19: chr21-26645083;