ENST00000520607.1:c.-229-1147T>C

Variant names:

• chr8-23099490-T-C
• rs12545733
• ENST00000520607.1:c.-229-1147T>C

Variant summary

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

The ENST00000520607.1(ENSG00000284956):​c.-229-1147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,866 control chromosomes in the GnomAD database, including 30,328 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 0.62 (30328 hom., cov: 30)
• Consequence: ENSG00000284956 ENST00000520607.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61
• Publications: 8 publications found

Genes affected

ENSG00000284956 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC254896	NR_046173.1	n.333-1147T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284956	ENST00000520607.1	c.-229-1147T>C		intron_variant	Intron 2 of 5	4		ENSP00000493787.1
ENSG00000284948	ENST00000397703.6	n.333-1147T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94529 AN: 151746 Hom.: 30334 Cov.: 30

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.623 AC: 94546 AN: 151866 Hom.: 30328 Cov.: 30 AF XY: 0.628 AC XY: 46606 AN XY: 74256

African (AFR) AF: 0.463 AC: 19157 AN: 41390

American (AMR) AF: 0.616 AC: 9402 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1979 AN: 3468

East Asian (EAS) AF: 0.701 AC: 3610 AN: 5152

South Asian (SAS) AF: 0.728 AC: 3498 AN: 4804

European-Finnish (FIN) AF: 0.703 AC: 7414 AN: 10552

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47371 AN: 67922

Other (OTH) AF: 0.624 AC: 1316 AN: 2108

Alfa AF: 0.538 Hom.: 1577

Bravo AF: 0.609

Asia WGS AF: 0.712 AC: 2478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.31
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12545733; hg19: chr8-22957003; COSMIC: COSV63512176; COSMIC: COSV63512176;