18-5555974-T-C

Variant names:

• chr18-5555974-T-C
• rs1941001
• NM_001384698.1:c.-305-66813A>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.-305-66813A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,018 control chromosomes in the GnomAD database, including 29,601 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 0.62 (29601 hom., cov: 32)
• Consequence: EPB41L3 NM_001384698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93719 AN: 151900 Hom.: 29587 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.617 AC: 93774 AN: 152018 Hom.: 29601 Cov.: 32 AF XY: 0.616 AC XY: 45770 AN XY: 74292

African (AFR) AF: 0.479 AC: 19854 AN: 41454

American (AMR) AF: 0.678 AC: 10359 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2077 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3237 AN: 5162

South Asian (SAS) AF: 0.555 AC: 2665 AN: 4806

European-Finnish (FIN) AF: 0.663 AC: 7002 AN: 10568

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46465 AN: 67954

Other (OTH) AF: 0.579 AC: 1223 AN: 2112

Alfa AF: 0.596 Hom.: 11761

Bravo AF: 0.613

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.19
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1941001; hg19: chr18-5555973;