12-57459370-G-C

Position:

• chr12-57459370-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000656936.1(ENSG00000287200):​n.268C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,218 control chromosomes in the GnomAD database, including 27,031 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 0.59 (26960 hom., cov: 30)
  • Exomes 𝑓: 0.63 (71 hom.)
• Consequence: ENST00000656936.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902947	XR_007063335.1	n.422C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000656936.1	n.268C>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89740 AN: 151736 Hom.: 26951 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.626 AC: 228 AN: 364 Hom.: 71 AF XY: 0.650 AC XY: 156 AN XY: 240

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.591 AC: 89764 AN: 151854 Hom.: 26960 Cov.: 30 AF XY: 0.584 AC XY: 43301 AN XY: 74200

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.625

Alfa AF: 0.474 Hom.: 1257

Bravo AF: 0.593

Asia WGS AF: 0.469 AC: 1634 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	6.9
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242578; hg19: chr12-57853153;