12-76004953-T-C

Variant names:

• chr12-76004953-T-C
• rs2367446
• ENST00000813240.1:n.192T>C

Variant summary

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

The ENST00000813240.1(ENSG00000257329):​n.192T>C 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 0.277 in 152,108 control chromosomes in the GnomAD database, including 6,793 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 0.28 (6793 hom., cov: 32)
• Consequence: ENSG00000257329 ENST00000813240.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 5 publications found

Genes affected

ENSG00000257329 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105369847	XR_945110.4	n.402+1236A>G		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257329	ENST00000813240.1	n.192T>C		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000305824	ENST00000813167.1	n.183+1236A>G		intron_variant	Intron 2 of 3
ENSG00000305824	ENST00000813168.1	n.267+1236A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42081 AN: 151990 Hom.: 6795 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.277 AC: 42061 AN: 152108 Hom.: 6793 Cov.: 32 AF XY: 0.282 AC XY: 20985 AN XY: 74342

African (AFR) AF: 0.113 AC: 4674 AN: 41512

American (AMR) AF: 0.274 AC: 4182 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2475 AN: 5160

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4820

European-Finnish (FIN) AF: 0.401 AC: 4237 AN: 10560

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

European-Non Finnish (NFE) AF: 0.340 AC: 23122 AN: 67990

Other (OTH) AF: 0.259 AC: 545 AN: 2108

Alfa AF: 0.317 Hom.: 6576

Bravo AF: 0.260

Asia WGS AF: 0.380 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.031
DANN	Benign	0.47
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2367446; hg19: chr12-76398733;