chr18-5560259-T-C

Variant names:

• chr18-5560259-T-C
• rs1785394
• NM_001384698.1:c.-306+70118A>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+70118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,142 control chromosomes in the GnomAD database, including 50,933 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 0.81 (50933 hom., cov: 32)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 4 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]

ENSG00000264000 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L3	NM_001384698.1	c.-306+70118A>G		intron_variant	Intron 1 of 21		NP_001371627.1
EPB41L3	NM_001384699.1	c.-306+70118A>G		intron_variant	Intron 1 of 20		NP_001371628.1
EPB41L3	NM_001384700.1	c.-306+70118A>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+52081A>G		intron_variant	Intron 3 of 21	2		ENSP00000488626.1
EPB41L3	ENST00000582592.1	c.55+17071A>G		intron_variant	Intron 1 of 2	5		ENSP00000463707.1
EPB41L3	ENST00000578431.1	n.324+70118A>G		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122930 AN: 152024 Hom.: 50906 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.809 AC: 123013 AN: 152142 Hom.: 50933 Cov.: 32 AF XY: 0.809 AC XY: 60199 AN XY: 74378

African (AFR) AF: 0.617 AC: 25600 AN: 41480

American (AMR) AF: 0.839 AC: 12831 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3039 AN: 3468

East Asian (EAS) AF: 0.767 AC: 3970 AN: 5174

South Asian (SAS) AF: 0.852 AC: 4104 AN: 4818

European-Finnish (FIN) AF: 0.859 AC: 9090 AN: 10582

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61567 AN: 68018

Other (OTH) AF: 0.810 AC: 1710 AN: 2110

Alfa AF: 0.881 Hom.: 96101

Bravo AF: 0.808

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1785394; hg19: chr18-5560258;