9-109176597-C-T

Variant names:

• chr9-109176597-C-T
• rs1831847098
• NM_019114.5:c.2587G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019114.5(EPB41L4B):​c.2587G>A​(p.Val863Met) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB41L4B NM_019114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• Publications: 0 publications found

Genes affected

EPB41L4B (HGNC:19818): (erythrocyte membrane protein band 4.1 like 4B) Predicted to be a structural constituent of cytoskeleton. Involved in several processes, including positive regulation of cell adhesion; positive regulation of keratinocyte migration; and wound healing. Acts upstream of or within actomyosin structure organization. Located in apical part of cell; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37965074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019114.5. 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
	EPB41L4B	NM_019114.5	MANE Select	c.2587G>A	p.Val863Met	missense	Exon 25 of 26	NP_061987.3
	EPB41L4B	NM_001385623.1		c.2479G>A	p.Val827Met	missense	Exon 24 of 25	NP_001372552.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4B	ENST00000374566.8	TSL:1 MANE Select	c.2587G>A	p.Val863Met	missense	Exon 25 of 26	ENSP00000363694.3	Q9H329-1
	EPB41L4B	ENST00000952218.1		c.2701G>A	p.Val901Met	missense	Exon 26 of 27	ENSP00000622277.1
	EPB41L4B	ENST00000952215.1		c.2596G>A	p.Val866Met	missense	Exon 25 of 26	ENSP00000622274.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	0.81	L
PhyloP100		3.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.65	N
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.087	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.26		Loss of sheet (P = 0.0228)
MVP		0.55
MPC		0.89
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.24
gMVP		0.40
Mutation Taster		=93/7	polymorphism

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: rs1831847098; hg19: chr9-111938877; COSMIC: COSV105308544;