chr12-47962326-A-G

Variant names:

• chr12-47962326-A-G
• rs4760673
• ENST00000624535.1:n.1144T>C

Variant summary

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

The ENST00000624535.1(ENSG00000279840):​n.1144T>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 0.251 in 152,112 control chromosomes in the GnomAD database, including 6,440 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 0.25 (6439 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: ENSG00000279840 ENST00000624535.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 8 publications found

Genes affected

ENSG00000279840 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000279840	ENST00000624535.1	n.1144T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38162 AN: 151952 Hom.: 6430 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.114 AC: 5 AN: 44 Hom.: 1 Cov.: 0 AF XY: 0.0938 AC XY: 3 AN XY: 32

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.147 AC: 5 AN: 34

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000102688), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.251 AC: 38204 AN: 152068 Hom.: 6439 Cov.: 32 AF XY: 0.246 AC XY: 18287 AN XY: 74350

African (AFR) AF: 0.479 AC: 19835 AN: 41438

American (AMR) AF: 0.191 AC: 2923 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3472

East Asian (EAS) AF: 0.286 AC: 1474 AN: 5154

South Asian (SAS) AF: 0.174 AC: 838 AN: 4826

European-Finnish (FIN) AF: 0.0998 AC: 1056 AN: 10580

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10818 AN: 67992

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.184 Hom.: 13445

Bravo AF: 0.267

Asia WGS AF: 0.239 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs4760673; hg19: chr12-48356109;