5-112169033-C-G

Variant names:

• chr5-112169033-C-G
• NM_022140.5:c.1812G>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.1812G>C​(p.Gln604His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EPB41L4A NM_022140.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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=0.20698053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.1812G>C	p.Gln604His	missense_variant	Exon 21 of 23	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.1812G>C	p.Gln604His	missense_variant	Exon 21 of 23	1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000507810.5	n.832G>C		non_coding_transcript_exon_variant	Exon 10 of 14	2
EPB41L4A	ENST00000509342.6	n.260G>C		non_coding_transcript_exon_variant	Exon 4 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1812G>C (p.Q604H) alteration is located in exon 21 (coding exon 21) of the EPB41L4A gene. This alteration results from a G to C substitution at nucleotide position 1812, causing the glutamine (Q) at amino acid position 604 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.85	D;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.20	.;N
REVEL	Benign	0.29
Sift	Uncertain	0.0050	.;D
Sift4G	Benign	0.14	T;T
Polyphen		0.076	B;B
Vest4		0.30
MutPred		0.13		Loss of solvent accessibility (P = 0.0576);Loss of solvent accessibility (P = 0.0576);
MVP		0.91
MPC		0.045
ClinPred		0.61	D
GERP RS		5.9
Varity_R		0.17
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-111504730;