rs11661706

Variant names:

• chr18-5419876-C-T
• rs11661706
• NM_012307.5:c.1341G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012307.5(EPB41L3):​c.1341G>A​(p.Glu447Glu) variant causes a splice region, synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EPB41L3 NM_012307.5 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	NM_012307.5	MANE Select	c.1341G>A	p.Glu447Glu	splice_region synonymous	Exon 12 of 23	NP_036439.2
	EPB41L3	NM_001384685.1		c.1395G>A	p.Glu465Glu	synonymous	Exon 12 of 23	NP_001371614.1
	EPB41L3	NM_001330557.2		c.1395G>A	p.Glu465Glu	synonymous	Exon 12 of 22	NP_001317486.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	ENST00000341928.7	TSL:1 MANE Select	c.1341G>A	p.Glu447Glu	splice_region synonymous	Exon 12 of 23	ENSP00000343158.2
	EPB41L3	ENST00000540638.6	TSL:1	c.1395G>A	p.Glu465Glu	synonymous	Exon 12 of 20	ENSP00000442091.2
	EPB41L3	ENST00000866153.1		c.1395G>A	p.Glu465Glu	synonymous	Exon 12 of 25	ENSP00000536212.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		4.7
PromoterAI		-0.0030	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs11661706; hg19: chr18-5419875; COSMIC: COSV59471494; COSMIC: COSV59471494;