18-5525038-C-T

Variant names:

• chr18-5525038-C-T
• rs1719953
• NM_012307.5:c.-12+18875G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012307.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	NM_012307.5	MANE Select	c.-12+18875G>A		intron	N/A	NP_036439.2
	EPB41L3	NM_001384685.1		c.-12+18875G>A		intron	N/A	NP_001371614.1
	EPB41L3	NM_001330557.2		c.-12+18875G>A		intron	N/A	NP_001317486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	ENST00000341928.7	TSL:1 MANE Select	c.-12+18875G>A		intron	N/A	ENSP00000343158.2
	EPB41L3	ENST00000540638.6	TSL:1	c.-12+18875G>A		intron	N/A	ENSP00000442091.2
	EPB41L3	ENST00000400111.8	TSL:5	c.-12+18875G>A		intron	N/A	ENSP00000382981.5

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

African (AFR) AF: 0.346 AC: 14337 AN: 41490

American (AMR) AF: 0.199 AC: 3047 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3472

East Asian (EAS) AF: 0.139 AC: 723 AN: 5184

South Asian (SAS) AF: 0.201 AC: 972 AN: 4828

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12546 AN: 68014

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.125 Hom.: 299

Bravo AF: 0.239

Asia WGS AF: 0.175 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.68
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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