rs12431592

Variant names:

• chr14-56677522-G-C
• rs12431592
• ENST00000554597.5:n.370-28394C>G

Variant summary

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

The ENST00000554597.5(ENSG00000259133):​n.370-28394C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,100 control chromosomes in the GnomAD database, including 21,936 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 0.49 (21936 hom., cov: 32)
• Consequence: ENSG00000259133 ENST00000554597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 3 publications found

Genes affected

ENSG00000259133 (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 (EAS) allele frequency at 95% confidence interval = 0.632 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
ENSG00000259133	ENST00000554597.5	n.370-28394C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75180 AN: 151982 Hom.: 21926 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.494 AC: 75202 AN: 152100 Hom.: 21936 Cov.: 32 AF XY: 0.499 AC XY: 37129 AN XY: 74360

African (AFR) AF: 0.166 AC: 6883 AN: 41480

American (AMR) AF: 0.524 AC: 8004 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1876 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3359 AN: 5166

South Asian (SAS) AF: 0.561 AC: 2707 AN: 4828

European-Finnish (FIN) AF: 0.678 AC: 7162 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43330 AN: 67986

Other (OTH) AF: 0.513 AC: 1085 AN: 2114

Alfa AF: 0.554 Hom.: 3164

Bravo AF: 0.472

Asia WGS AF: 0.592 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.31
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs12431592; hg19: chr14-57144240;