12-97245366-A-G

Variant names:

• chr12-97245366-A-G
• rs1012315
• ENST00000778372.1:n.248+7402T>C

Variant summary

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

The ENST00000778372.1(ENSG00000301349):​n.248+7402T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 517,280 control chromosomes in the GnomAD database, including 118,212 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 0.64 (32297 hom., cov: 32)
  • Exomes 𝑓: 0.68 (85915 hom.)
• Consequence: ENSG00000301349 ENST00000778372.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801
• Publications: 9 publications found

Genes affected

ENSG00000301349 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101928912	XR_246024.4	n.223+7402T>C		intron_variant	Intron 2 of 2
LOC101928912	XR_945251.3	n.224-1644T>C		intron_variant	Intron 2 of 3
LOC101928912	XR_945252.3	n.224-4304T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301349	ENST00000778372.1	n.248+7402T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97551 AN: 151756 Hom.: 32292 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.692

GnomAD2 exomes AF: 0.677 AC: 154159 AN: 227740 AF XY: 0.677

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.793

Gnomad EAS exome AF: 0.672

Gnomad FIN exome AF: 0.685

Gnomad NFE exome AF: 0.730

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.680 AC: 248546 AN: 365406 Hom.: 85915 Cov.: 0 AF XY: 0.671 AC XY: 140734 AN XY: 209604

African (AFR) AF: 0.474 AC: 4900 AN: 10332

American (AMR) AF: 0.669 AC: 24185 AN: 36154

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 9334 AN: 11694

East Asian (EAS) AF: 0.678 AC: 8886 AN: 13102

South Asian (SAS) AF: 0.556 AC: 37009 AN: 66580

European-Finnish (FIN) AF: 0.694 AC: 11671 AN: 16828

Middle Eastern (MID) AF: 0.732 AC: 2080 AN: 2842

European-Non Finnish (NFE) AF: 0.726 AC: 138819 AN: 191326

Other (OTH) AF: 0.705 AC: 11662 AN: 16548

GnomAD4 genome AF: 0.643 AC: 97601 AN: 151874 Hom.: 32297 Cov.: 32 AF XY: 0.641 AC XY: 47597 AN XY: 74206

African (AFR) AF: 0.481 AC: 19942 AN: 41432

American (AMR) AF: 0.671 AC: 10224 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2734 AN: 3470

East Asian (EAS) AF: 0.669 AC: 3435 AN: 5134

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4824

European-Finnish (FIN) AF: 0.676 AC: 7123 AN: 10542

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49044 AN: 67918

Other (OTH) AF: 0.690 AC: 1454 AN: 2108

Alfa AF: 0.705 Hom.: 182548

Bravo AF: 0.641

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs1012315; hg19: chr12-97639144; COSMIC: COSV67304688;