21-22418908-G-A

Variant names:

• chr21-22418908-G-A
• rs4818677
• ENST00000444130.1:n.386-1862G>A

Variant summary

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

The ENST00000732680.1(ENSG00000295777):​n.259-16699C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,000 control chromosomes in the GnomAD database, including 64,254 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 0.92 (64254 hom., cov: 32)
• Consequence: ENSG00000295777 ENST00000732680.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 0 publications found

Genes affected

ENSG00000226043 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000732680.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000226043	ENST00000444130.1	TSL:5	n.386-1862G>A		intron	N/A
	ENSG00000295777	ENST00000732680.1		n.259-16699C>T		intron	N/A
	ENSG00000295777	ENST00000732681.1		n.324+12041C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139402 AN: 151882 Hom.: 64219 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.929

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.918 AC: 139493 AN: 152000 Hom.: 64254 Cov.: 32 AF XY: 0.920 AC XY: 68372 AN XY: 74332

African (AFR) AF: 0.828 AC: 34352 AN: 41486

American (AMR) AF: 0.952 AC: 14519 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3292 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5186

South Asian (SAS) AF: 0.948 AC: 4574 AN: 4826

European-Finnish (FIN) AF: 0.963 AC: 10182 AN: 10574

Middle Eastern (MID) AF: 0.931 AC: 270 AN: 290

European-Non Finnish (NFE) AF: 0.947 AC: 64296 AN: 67898

Other (OTH) AF: 0.925 AC: 1953 AN: 2112

Alfa AF: 0.928 Hom.: 9323

Bravo AF: 0.914

Asia WGS AF: 0.958 AC: 3294 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.18
PhyloP100		0.74

Splicing

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

Other links and lift over

dbSNP: rs4818677; hg19: chr21-23791228;