12-75670748-T-C

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000552856.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258077	ENST00000552856.1	TSL:3	n.401+21357A>G		intron	N/A
	ENSG00000286259	ENST00000651075.1		n.262-88T>C		intron	N/A
	ENSG00000258077	ENST00000741371.1		n.527+21357A>G		intron	N/A

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 v4.9

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;