chr18-5525038-C-G

Variant names:

• chr18-5525038-C-G
• rs1719953
• NM_012307.5:c.-12+18875G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012307.5(EPB41L3):​c.-12+18875G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.-12+18875G>C		intron	N/A	NP_036439.2
	EPB41L3	NM_001384685.1		c.-12+18875G>C		intron	N/A	NP_001371614.1
	EPB41L3	NM_001330557.2		c.-12+18875G>C		intron	N/A	NP_001317486.1	A0A0A0MRA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L3	ENST00000341928.7	TSL:1 MANE Select	c.-12+18875G>C		intron	N/A	ENSP00000343158.2	Q9Y2J2-1
	EPB41L3	ENST00000540638.6	TSL:1	c.-12+18875G>C		intron	N/A	ENSP00000442091.2	Q9Y2J2-2
	EPB41L3	ENST00000866153.1		c.-12+18875G>C		intron	N/A	ENSP00000536212.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.49
PhyloP100		-0.48

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: rs1719953; hg19: chr18-5525037;