12-91454361-T-C

Variant summary

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

The ENST00000685093.1(ENSG00000289605):n.674+52350A>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 0.438 in 151,938 control chromosomes in the GnomAD database, including 14,749 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 0.44 (14749 hom., cov: 32)
• Consequence: ENST00000685093.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105369896	XR_001749251.2	n.3841+52350A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000685093.1	n.674+52350A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66516 AN: 151818 Hom.: 14734 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.438 AC: 66582 AN: 151938 Hom.: 14749 Cov.: 32 AF XY: 0.434 AC XY: 32218 AN XY: 74244

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.475

Alfa AF: 0.447 Hom.: 1752

Bravo AF: 0.439

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	15
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2034954; hg19: chr12-91848138;