Variant 5-112184127-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022140.5(EPB41L4A):c.1511A>G(p.Gln504Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EPB41L4A
NM_022140.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.24466833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5 link	c.1511A>G	p.Gln504Arg	missense_variant	18/23	ENST00000261486.6	NP_071423.4	Q9HCS5Q8NEH8Q8N8X1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EPB41L4A	ENST00000261486.6 link	c.1511A>G	p.Gln504Arg	missense_variant	18/23	1	NM_022140.5	ENSP00000261486.5	Q9HCS5
EPB41L4A	ENST00000507810.5 link	n.531A>G		non_coding_transcript_exon_variant	7/14	2
EPB41L4A	ENST00000515047.5 link	n.331A>G		non_coding_transcript_exon_variant	5/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249378

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2024

The c.1511A>G (p.Q504R) 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 1511, causing the glutamine (Q) at amino acid position 504 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.041

Eigen_PC

Benign

0.078

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

D;.

M_CAP

Benign

0.052

MetaRNN

Benign

0.24

T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.27

.;N

REVEL

Uncertain

0.35

Sift

Benign

0.14

.;T

Sift4G

Benign

0.41

T;T

Polyphen

0.11

B;B

Vest4

0.51

MutPred

0.19

Gain of MoRF binding (P = 0.2114);Gain of MoRF binding (P = 0.2114);

MVP

0.79

MPC

0.046

ClinPred

0.30

GERP RS

3.7

Varity_R

0.11

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over