5-112184052-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022140.5(EPB41L4A):c.1586A>G(p.Asp529Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: EPB41L4A NM_022140.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.70

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3736092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5	c.1586A>G	p.Asp529Gly	missense_variant	18/23	ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.1586A>G	p.Asp529Gly	missense_variant	18/23	1	NM_022140.5	P1
EPB41L4A	ENST00000507810.5	n.606A>G		non_coding_transcript_exon_variant	7/14	2
EPB41L4A	ENST00000515047.5	n.406A>G		non_coding_transcript_exon_variant	5/7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461770 Hom.: 0 Cov.: 34 AF XY: 0.0000261 AC XY: 19 AN XY: 727182

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: 0.0000324

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.1586A>G (p.D529G) alteration is located in exon 18 (coding exon 18) of the EPB41L4A gene. This alteration results from a A to G substitution at nucleotide position 1586, causing the aspartic acid (D) at amino acid position 529 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.11	T;T
Polyphen		0.31	B;B
Vest4		0.53
MutPred		0.17		Loss of stability (P = 0.0518);Loss of stability (P = 0.0518);
MVP		0.89
MPC		0.11
ClinPred		0.71	D
GERP RS		6.2
Varity_R		0.25
gMVP		0.47

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: chr5-111519749;