5-112168747-C-G

Variant names:

• chr5-112168747-C-G
• rs180931108
• NM_022140.5:c.1924G>C

Variant summary

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

The NM_022140.5(EPB41L4A):​c.1924G>C​(p.Val642Leu) 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. 15/21 in silico tools predict 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: EPB41L4A NM_022140.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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]

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=0.07656571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.1924G>C	p.Val642Leu	missense_variant	Exon 22 of 23	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.1924G>C	p.Val642Leu	missense_variant	Exon 22 of 23	1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000507810.5	n.944G>C		non_coding_transcript_exon_variant	Exon 11 of 14	2
EPB41L4A	ENST00000509342.6	n.372G>C		non_coding_transcript_exon_variant	Exon 5 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0082	T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.68	T;.
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.16	.;N
REVEL	Benign	0.25
Sift	Benign	0.075	.;T
Sift4G	Benign	0.37	T;T
Polyphen		0.020	B;B
Vest4		0.13
MutPred		0.23		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.69
MPC		0.044
ClinPred		0.17	T
GERP RS		4.7
Varity_R		0.099
gMVP		0.27

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: rs180931108; hg19: chr5-111504444;