21-22259356-G-T

Variant names:

• chr21-22259356-G-T
• rs2827312
• ENST00000444130.1:n.385+46543G>T

Variant summary

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

The ENST00000654607.1(ENSG00000226043):​n.404+46543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,954 control chromosomes in the GnomAD database, including 10,261 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 0.36 (10261 hom., cov: 32)
• Consequence: ENSG00000226043 ENST00000654607.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 14 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000654607.1. 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.385+46543G>T		intron	N/A
	ENSG00000226043	ENST00000654607.1		n.404+46543G>T		intron	N/A
	ENSG00000226043	ENST00000667099.1		n.404+46543G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54906 AN: 151836 Hom.: 10266 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.361 AC: 54922 AN: 151954 Hom.: 10261 Cov.: 32 AF XY: 0.357 AC XY: 26537 AN XY: 74262

African (AFR) AF: 0.361 AC: 14949 AN: 41412

American (AMR) AF: 0.393 AC: 6000 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1505 AN: 3472

East Asian (EAS) AF: 0.0895 AC: 463 AN: 5174

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4824

European-Finnish (FIN) AF: 0.319 AC: 3363 AN: 10538

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25737 AN: 67952

Other (OTH) AF: 0.393 AC: 830 AN: 2110

Alfa AF: 0.371 Hom.: 40064

Bravo AF: 0.367

Asia WGS AF: 0.191 AC: 665 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.46
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2827312; hg19: chr21-23631676;