5-112194587-A-G

Position:

• chr5-112194587-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022140.5(EPB41L4A):​c.1483T>C​(p.Tyr495His) variant causes a missense change. The variant allele was found at a frequency of 0.736 in 1,593,080 control chromosomes in the GnomAD database, including 436,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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: 𝑓 0.78 (47390 hom., cov: 32)
  • Exomes 𝑓: 0.73 (389252 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7763503E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.1483T>C	p.Tyr495His	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>C	p.Tyr495His	missense_variant	17/23	1	NM_022140.5	ENSP00000261486.5

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119175 AN: 152054 Hom.: 47338 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.790

GnomAD3 exomes AF: 0.784 AC: 188472 AN: 240312 Hom.: 75133 AF XY: 0.780 AC XY: 101705 AN XY: 130402

Gnomad AFR exome AF: 0.881

Gnomad AMR exome AF: 0.870

Gnomad ASJ exome AF: 0.755

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.857

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.731 AC: 1053659 AN: 1440908 Hom.: 389252 Cov.: 26 AF XY: 0.734 AC XY: 526586 AN XY: 717326

Gnomad4 AFR exome AF: 0.879

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.755

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.854

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.755

GnomAD4 genome AF: 0.784 AC: 119287 AN: 152172 Hom.: 47390 Cov.: 32 AF XY: 0.790 AC XY: 58746 AN XY: 74394

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.793

Alfa AF: 0.724 Hom.: 91122

Bravo AF: 0.792

TwinsUK AF: 0.719 AC: 2665

ALSPAC AF: 0.689 AC: 2656

ESP6500AA AF: 0.879 AC: 3185

ESP6500EA AF: 0.713 AC: 5805

ExAC AF: 0.785 AC: 94822

Asia WGS AF: 0.933 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.0045	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.052	T;.
MetaRNN	Benign	5.8e-7	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.3	.;N
REVEL	Uncertain	0.33
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.23
MPC		0.049
ClinPred		0.0067	T
GERP RS		5.1
Varity_R		0.057
gMVP		0.39

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;