rs7719346

Positions:

• chr5-112194587-A-C
• chr5-112194587-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022140.5(EPB41L4A):​c.1483T>G​(p.Tyr495Asp) variant causes a missense change. 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: EPB41L4A NM_022140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38

Genes affected

EPB41L4A (HGNC:13278): (erythrocyte membrane protein band 4.1 like 4A) The protein encoded by this gene is a member of the band 4.1 protein superfamily. Members of this superfamily are thought to play an important role in regulating interactions between the cytoskeleton and plasma membrane, and contain an amino terminal conserved domain that binds glycophorin C. This gene product is thought to be involved in the beta-catenin signaling pathway. [provided by RefSeq, Dec 2016]

EPB41L4A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13450572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.1483T>G	p.Tyr495Asp	missense_variant	17/23	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.1483T>G	p.Tyr495Asp	missense_variant	17/23	1	NM_022140.5	ENSP00000261486.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.35	T;.
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.0	B;B
Vest4		0.30
MutPred		0.17		Gain of ubiquitination at K498 (P = 0.0232);Gain of ubiquitination at K498 (P = 0.0232);
MVP		0.86
MPC		0.063
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.29
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs7719346; hg19: chr5-111530284;