rs4798376

Variant names:

• chr18-5604241-T-C
• rs4798376
• NM_001384698.1:c.-306+26136A>G

Variant summary

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

The NM_001384698.1(EPB41L3):​c.-306+26136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 150,946 control chromosomes in the GnomAD database, including 6,065 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 0.28 (6065 hom., cov: 30)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L3	NM_001384698.1	c.-306+26136A>G		intron_variant	Intron 1 of 21		NP_001371627.1
EPB41L3	NM_001384699.1	c.-306+26136A>G		intron_variant	Intron 1 of 20		NP_001371628.1
EPB41L3	NM_001384700.1	c.-306+26136A>G		intron_variant	Intron 1 of 21		NP_001371629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-306+8099A>G		intron_variant	Intron 3 of 21	2		ENSP00000488626.1
EPB41L3	ENST00000578431.1	n.324+26136A>G		intron_variant	Intron 1 of 2	2
EPB41L3	ENST00000637651.1	n.-306+26136A>G		intron_variant	Intron 1 of 21	5		ENSP00000489681.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41845 AN: 150828 Hom.: 6040 Cov.: 30

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.278 AC: 41907 AN: 150946 Hom.: 6065 Cov.: 30 AF XY: 0.281 AC XY: 20699 AN XY: 73688

African (AFR) AF: 0.245 AC: 10028 AN: 41010

American (AMR) AF: 0.417 AC: 6309 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 722 AN: 3450

East Asian (EAS) AF: 0.531 AC: 2695 AN: 5080

South Asian (SAS) AF: 0.292 AC: 1378 AN: 4724

European-Finnish (FIN) AF: 0.245 AC: 2551 AN: 10416

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17310 AN: 67812

Other (OTH) AF: 0.281 AC: 590 AN: 2102

Alfa AF: 0.264 Hom.: 10070

Bravo AF: 0.291

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs4798376; hg19: chr18-5604240;