18-5525038-C-T

Position:

• chr18-5525038-C-T

Variant summary

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

The NM_012307.5(EPB41L3):​c.-12+18875G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,200 control chromosomes in the GnomAD database, including 4,373 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 0.23 (4373 hom., cov: 33)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

Genes affected

EPB41L3 (HGNC:3380): (erythrocyte membrane protein band 4.1 like 3) Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to paranode region of axon. Located in cell-cell junction and plasma membrane. Biomarker of meningioma. [provided by Alliance of Genome Resources, Apr 2022]

EPB41L3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L3	NM_012307.5	c.-12+18875G>A		intron_variant		ENST00000341928.7	NP_036439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000341928.7	c.-12+18875G>A		intron_variant		1	NM_012307.5	ENSP00000343158.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34366 AN: 152082 Hom.: 4368 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.226 AC: 34407 AN: 152200 Hom.: 4373 Cov.: 33 AF XY: 0.221 AC XY: 16436 AN XY: 74420

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.230

Alfa AF: 0.117 Hom.: 248

Bravo AF: 0.239

Asia WGS AF: 0.175 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1719953; hg19: chr18-5525037; COSMIC: COSV59456432; COSMIC: COSV59456432;