22-23892477-T-C

Variant names:

• chr22-23892477-T-C
• rs2012124
• ENST00000433835.3:c.432-2295T>C

Variant summary

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

The ENST00000433835.3(ENSG00000251357):​c.432-2295T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,980 control chromosomes in the GnomAD database, including 45,321 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 (45321 hom., cov: 30)
• Consequence: ENSG00000251357 ENST00000433835.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.968
• Publications: 16 publications found

Genes affected

ENSG00000251357 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433835.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000251357	ENST00000433835.3	TSL:5	c.432-2295T>C		intron	N/A	ENSP00000400325.3	H7C1H1
	ENSG00000290199	ENST00000717616.1		n.213-1011A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117150 AN: 151862 Hom.: 45280 Cov.: 30

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.771 AC: 117247 AN: 151980 Hom.: 45321 Cov.: 30 AF XY: 0.773 AC XY: 57458 AN XY: 74292

African (AFR) AF: 0.809 AC: 33496 AN: 41402

American (AMR) AF: 0.789 AC: 12063 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2523 AN: 3468

East Asian (EAS) AF: 0.655 AC: 3386 AN: 5172

South Asian (SAS) AF: 0.766 AC: 3673 AN: 4796

European-Finnish (FIN) AF: 0.791 AC: 8366 AN: 10578

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51072 AN: 67964

Other (OTH) AF: 0.759 AC: 1601 AN: 2110

Alfa AF: 0.757 Hom.: 43311

Bravo AF: 0.774

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.31
PhyloP100		-0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2012124;

hg19: chr22-24234664;