rs12582659

Variant names:

• chr12-75670748-T-C
• rs12582659
• ENST00000552856.1:n.401+21357A>G

Variant summary

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

The ENST00000552856.1(ENSG00000258077):​n.401+21357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,336 control chromosomes in the GnomAD database, including 512 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 0.054 (512 hom., cov: 33)
• Consequence: ENSG00000258077 ENST00000552856.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 5 publications found

Genes affected

ENSG00000258077 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369844	XR_007063374.1	n.691+21357A>G		intron_variant	Intron 5 of 6
LOC105369844	XR_007063375.1	n.1372-6942A>G		intron_variant	Intron 6 of 15
LOC105369844	XR_007063376.1	n.2299-6942A>G		intron_variant	Intron 4 of 7
LOC105369844	XR_007063377.1	n.2299-6942A>G		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258077	ENST00000552856.1	n.401+21357A>G		intron_variant	Intron 3 of 4	3
ENSG00000286259	ENST00000651075.1	n.262-88T>C		intron_variant	Intron 3 of 5
ENSG00000258077	ENST00000741371.1	n.527+21357A>G		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8256 AN: 152218 Hom.: 507 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00883

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0543 AC: 8276 AN: 152336 Hom.: 512 Cov.: 33 AF XY: 0.0590 AC XY: 4392 AN XY: 74500

African (AFR) AF: 0.104 AC: 4343 AN: 41572

American (AMR) AF: 0.0218 AC: 334 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1129 AN: 5184

South Asian (SAS) AF: 0.195 AC: 943 AN: 4824

European-Finnish (FIN) AF: 0.0678 AC: 720 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00883 AC: 601 AN: 68038

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0361 Hom.: 124

Bravo AF: 0.0518

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.87
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs12582659; hg19: chr12-76064528;