8-137973680-A-G

Position:

• chr8-137973680-A-G

Variant summary

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

The ENST00000518973.1(ENSG00000253288):​n.514+109377T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,944 control chromosomes in the GnomAD database, including 17,804 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 0.47 (17804 hom., cov: 32)
• Consequence: ENSG00000253288 ENST00000518973.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

Genes affected

ENSG00000253288 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC401478	NR_161374.1	n.573+66659T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000253288	ENST00000518973.1	n.514+109377T>C		intron_variant		2
ENSG00000253288	ENST00000657186.1	n.601+109377T>C		intron_variant
ENSG00000254361	ENST00000667239.1	n.533-44123A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70779 AN: 151826 Hom.: 17801 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.466 AC: 70806 AN: 151944 Hom.: 17804 Cov.: 32 AF XY: 0.476 AC XY: 35306 AN XY: 74216

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.471

Alfa AF: 0.468 Hom.: 5519

Bravo AF: 0.460

Asia WGS AF: 0.774 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4373552; hg19: chr8-138985923;