rs4761659

Variant names:

• chr12-93293308-T-C
• rs4761659
• ENST00000754393.1:n.323+34719A>G

Variant summary

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

The ENST00000754393.1(ENSG00000257252):​n.323+34719A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,154 control chromosomes in the GnomAD database, including 60,010 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 0.89 (60010 hom., cov: 31)
• Consequence: ENSG00000257252 ENST00000754393.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 4 publications found

Genes affected

ENSG00000257252 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC643339	NR_040096.1	n.329+34719A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257252	ENST00000754393.1	n.323+34719A>G		intron_variant	Intron 2 of 7
ENSG00000257252	ENST00000754394.1	n.156-26552A>G		intron_variant	Intron 2 of 8
ENSG00000257252	ENST00000754396.1	n.232+22074A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134967 AN: 152036 Hom.: 59965 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.888 AC: 135068 AN: 152154 Hom.: 60010 Cov.: 31 AF XY: 0.884 AC XY: 65779 AN XY: 74390

African (AFR) AF: 0.910 AC: 37767 AN: 41504

American (AMR) AF: 0.859 AC: 13132 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3077 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4283 AN: 5174

South Asian (SAS) AF: 0.835 AC: 4025 AN: 4822

European-Finnish (FIN) AF: 0.892 AC: 9432 AN: 10576

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60436 AN: 68008

Other (OTH) AF: 0.883 AC: 1862 AN: 2108

Alfa AF: 0.888 Hom.: 111257

Bravo AF: 0.888

Asia WGS AF: 0.838 AC: 2915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.57
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs4761659; hg19: chr12-93687084;