22-39274846-G-T

Variant names:

• chr22-39274846-G-T
• rs968451
• ENST00000641859.1:n.110-1730G>T

Variant summary

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

The ENST00000641859.1(ENSG00000284633):​n.110-1730G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,022 control chromosomes in the GnomAD database, including 4,025 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 0.19 (4025 hom., cov: 31)
• Consequence: ENSG00000284633 ENST00000641859.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 38 publications found

Genes affected

ENSG00000284633 (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 (EAS) allele frequency at 95% confidence interval = 0.727 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
ENSG00000284633	ENST00000641859.1	n.110-1730G>T		intron_variant	Intron 1 of 2
ENSG00000284633	ENST00000642075.1	n.383-1730G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28912 AN: 151904 Hom.: 4028 Cov.: 31

Gnomad AFR AF: 0.0716

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.190 AC: 28912 AN: 152022 Hom.: 4025 Cov.: 31 AF XY: 0.201 AC XY: 14906 AN XY: 74264

African (AFR) AF: 0.0714 AC: 2966 AN: 41512

American (AMR) AF: 0.260 AC: 3976 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3468

East Asian (EAS) AF: 0.747 AC: 3849 AN: 5152

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4812

European-Finnish (FIN) AF: 0.291 AC: 3070 AN: 10532

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12767 AN: 67958

Other (OTH) AF: 0.193 AC: 406 AN: 2106

Alfa AF: 0.201 Hom.: 13978

Bravo AF: 0.186

Asia WGS AF: 0.462 AC: 1606 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	4.2
DANN	Benign	0.73
PhyloP100		0.016

Splicing

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

Other links and lift over

dbSNP: rs968451; hg19: chr22-39670851;