rs4798376

Positions:

• chr18-5604241-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EPB41L3	NM_001281535.2	c.-306+8099A>G		intron_variant			NP_001268464.1
EPB41L3	NM_001384683.1	c.-306+26136A>G		intron_variant			NP_001371612.1
EPB41L3	NM_001384698.1	c.-306+26136A>G		intron_variant			NP_001371627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000545076.5	c.-306+8099A>G		intron_variant		2		ENSP00000488626
EPB41L3	ENST00000637651.1	c.-306+26136A>G		intron_variant, NMD_transcript_variant		5		ENSP00000489681
EPB41L3	ENST00000578431.1	n.324+26136A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.281

Alfa AF: 0.258 Hom.: 6881

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4798376; hg19: chr18-5604240;