8-137973680-A-G

Variant names:

• chr8-137973680-A-G
• rs4373552
• ENST00000518973.1:n.514+109377T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

Genes affected

ENSG00000253288 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518973.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC401478	NR_161374.1		n.573+66659T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000253288	ENST00000518973.1	TSL:2	n.514+109377T>C		intron	N/A
	ENSG00000253288	ENST00000657186.1		n.601+109377T>C		intron	N/A
	ENSG00000254361	ENST00000667239.1		n.533-44123A>G		intron	N/A

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

African (AFR) AF: 0.321 AC: 13290 AN: 41444

American (AMR) AF: 0.535 AC: 8165 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1847 AN: 3466

East Asian (EAS) AF: 0.987 AC: 5082 AN: 5148

South Asian (SAS) AF: 0.664 AC: 3195 AN: 4810

European-Finnish (FIN) AF: 0.511 AC: 5392 AN: 10552

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32290 AN: 67958

Other (OTH) AF: 0.471 AC: 993 AN: 2108

Alfa AF: 0.464 Hom.: 6733

Bravo AF: 0.460

Asia WGS AF: 0.774 AC: 2692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		0.32

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4373552;

hg19: chr8-138985923;