18-5479094-A-G

Variant names:

• chr18-5479094-A-G
• rs7238186
• NM_012307.5:c.184-656T>C

Variant summary

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

The NM_012307.5(EPB41L3):​c.184-656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,264 control chromosomes in the GnomAD database, including 4,087 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 0.22 (4087 hom., cov: 33)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 6 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]

ENSG00000265316 (HGNC:58202):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 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.184-656T>C		intron	N/A	NP_036439.2
	EPB41L3	NM_001384685.1		c.184-656T>C		intron	N/A	NP_001371614.1
	EPB41L3	NM_001330557.2		c.184-656T>C		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.184-656T>C		intron	N/A	ENSP00000343158.2
	EPB41L3	ENST00000540638.6	TSL:1	c.184-656T>C		intron	N/A	ENSP00000442091.2
	EPB41L3	ENST00000400111.8	TSL:5	c.184-656T>C		intron	N/A	ENSP00000382981.5

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34234 AN: 152146 Hom.: 4088 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.225 AC: 34239 AN: 152264 Hom.: 4087 Cov.: 33 AF XY: 0.222 AC XY: 16494 AN XY: 74450

African (AFR) AF: 0.168 AC: 6973 AN: 41558

American (AMR) AF: 0.221 AC: 3386 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3470

East Asian (EAS) AF: 0.0692 AC: 359 AN: 5188

South Asian (SAS) AF: 0.249 AC: 1204 AN: 4826

European-Finnish (FIN) AF: 0.228 AC: 2413 AN: 10594

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17924 AN: 68022

Other (OTH) AF: 0.250 AC: 527 AN: 2108

Alfa AF: 0.256 Hom.: 7292

Bravo AF: 0.221

Asia WGS AF: 0.181 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		0.32
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: rs7238186; hg19: chr18-5479093;