12-74625974-C-T

Variant names:

• chr12-74625974-C-T
• rs822814
• ENST00000748205.1:n.178+6537C>T

Variant summary

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

The ENST00000748205.1(ENSG00000297480):​n.178+6537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,644 control chromosomes in the GnomAD database, including 36,074 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 0.68 (36074 hom., cov: 32)
• Consequence: ENSG00000297480 ENST00000748205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

Genes affected

ENSG00000297480 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 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
ENSG00000297480	ENST00000748205.1	n.178+6537C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103185 AN: 151528 Hom.: 36056 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.681 AC: 103240 AN: 151644 Hom.: 36074 Cov.: 32 AF XY: 0.690 AC XY: 51091 AN XY: 74082

African (AFR) AF: 0.537 AC: 22216 AN: 41400

American (AMR) AF: 0.747 AC: 11333 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2147 AN: 3454

East Asian (EAS) AF: 0.962 AC: 4942 AN: 5136

South Asian (SAS) AF: 0.866 AC: 4172 AN: 4818

European-Finnish (FIN) AF: 0.770 AC: 8147 AN: 10582

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 47906 AN: 67766

Other (OTH) AF: 0.684 AC: 1443 AN: 2110

Alfa AF: 0.667 Hom.: 4819

Bravo AF: 0.670

Asia WGS AF: 0.870 AC: 3022 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.29
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs822814; hg19: chr12-75019754;