rs746265

Variant names:

• chr15-39284359-A-C
• rs746265
• ENST00000558209.1:n.451+75430T>G

Variant summary

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

The ENST00000558209.1(ENSG00000259345):​n.451+75430T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,100 control chromosomes in the GnomAD database, including 3,642 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 (3642 hom., cov: 32)
• Consequence: ENSG00000259345 ENST00000558209.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 5 publications found

Genes affected

ENSG00000259345 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558209.1. 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
	ENSG00000259345	ENST00000558209.1	TSL:3	n.451+75430T>G		intron	N/A
	ENSG00000259345	ENST00000560484.1	TSL:4	n.67+136550T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29223 AN: 151982 Hom.: 3637 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.192 AC: 29258 AN: 152100 Hom.: 3642 Cov.: 32 AF XY: 0.188 AC XY: 13970 AN XY: 74358

African (AFR) AF: 0.364 AC: 15097 AN: 41432

American (AMR) AF: 0.110 AC: 1682 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3472

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5186

South Asian (SAS) AF: 0.0977 AC: 471 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9259 AN: 67998

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.161 Hom.: 3789

Bravo AF: 0.199

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		0.095

Splicing

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: rs746265;

hg19: chr15-39576560;