12-56114625-G-C

Variant names:

• chr12-56114625-G-C
• rs4759228
• ENST00000716007.1:n.756+1873C>G

Variant summary

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

The ENST00000716007.1(ENSG00000258317):​n.756+1873C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,078 control chromosomes in the GnomAD database, including 3,946 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 0.21 (3946 hom., cov: 31)
• Consequence: ENSG00000258317 ENST00000716007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 20 publications found

Genes affected

ENSG00000258317 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 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
ENSG00000258317	ENST00000716007.1	n.756+1873C>G		intron_variant	Intron 4 of 4
ENSG00000258317	ENST00000732776.1	n.905+1873C>G		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32053 AN: 151960 Hom.: 3945 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.211 AC: 32066 AN: 152078 Hom.: 3946 Cov.: 31 AF XY: 0.206 AC XY: 15304 AN XY: 74338

African (AFR) AF: 0.103 AC: 4251 AN: 41472

American (AMR) AF: 0.187 AC: 2856 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.0714 AC: 370 AN: 5182

South Asian (SAS) AF: 0.180 AC: 867 AN: 4824

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10580

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19409 AN: 67970

Other (OTH) AF: 0.234 AC: 493 AN: 2110

Alfa AF: 0.244 Hom.: 592

Bravo AF: 0.205

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.63
PhyloP100		-0.044

Splicing

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

Other links and lift over

dbSNP: rs4759228; hg19: chr12-56508409;