12-8452666-T-C

Position:

• chr12-8452666-T-C

Variant summary

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

The ENST00000693495.1(ENSG00000288954):​n.83+345A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,108 control chromosomes in the GnomAD database, including 6,983 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 0.30 (6983 hom., cov: 32)
• Consequence: ENST00000693495.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000693495.1	n.83+345A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45110 AN: 151990 Hom.: 6974 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.297 AC: 45151 AN: 152108 Hom.: 6983 Cov.: 32 AF XY: 0.300 AC XY: 22292 AN XY: 74364

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.287

Alfa AF: 0.254 Hom.: 1278

Bravo AF: 0.290

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11045418; hg19: chr12-8605262;