18-5555974-T-G

Variant names:

• chr18-5555974-T-G
• rs1941001
• NM_001384698.1:c.-305-66813A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384698.1(EPB41L3):​c.-305-66813A>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: 32)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

LOC107985145 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L3	NM_001384698.1	c.-305-66813A>C		intron_variant	Intron 1 of 21		NP_001371627.1
EPB41L3	NM_001384699.1	c.-305-66813A>C		intron_variant	Intron 1 of 20		NP_001371628.1
EPB41L3	NM_001384700.1	c.-305-66813A>C		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+56366A>C		intron_variant	Intron 3 of 21	2		ENSP00000488626.1
EPB41L3	ENST00000582592.1	c.55+21356A>C		intron_variant	Intron 1 of 2	5		ENSP00000463707.1
EPB41L3	ENST00000578431.1	n.325-66813A>C		intron_variant	Intron 1 of 2	2
EPB41L3	ENST00000637651.1	n.-305-66813A>C		intron_variant	Intron 1 of 21	5		ENSP00000489681.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.091
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1941001; hg19: chr18-5555973;