chr5-112194587-A-G

Variant names:

• chr5-112194587-A-G
• rs7719346
• NM_022140.5:c.1483T>C

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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: 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
• Publications: 28 publications found

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]

ENSG00000251187 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4A	NM_022140.5	MANE Select	c.1483T>C	p.Tyr495His	missense	Exon 17 of 23	NP_071423.4
	EPB41L4A	NM_001347887.2		c.1483T>C	p.Tyr495His	missense	Exon 17 of 24	NP_001334816.1
	EPB41L4A	NR_144931.2		n.1721T>C		non_coding_transcript_exon	Exon 17 of 23

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4A	ENST00000261486.6	TSL:1 MANE Select	c.1483T>C	p.Tyr495His	missense	Exon 17 of 23	ENSP00000261486.5
	EPB41L4A	ENST00000507810.5	TSL:2	n.503T>C		non_coding_transcript_exon	Exon 6 of 14
	EPB41L4A	ENST00000515047.5	TSL:3	n.303T>C		non_coding_transcript_exon	Exon 4 of 7

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

GnomAD2 exomes AF: 0.784 AC: 188472 AN: 240312 AF XY: 0.780

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 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

African (AFR) AF: 0.879 AC: 28803 AN: 32768

American (AMR) AF: 0.863 AC: 37254 AN: 43172

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 19503 AN: 25838

East Asian (EAS) AF: 0.999 AC: 39102 AN: 39158

South Asian (SAS) AF: 0.854 AC: 71602 AN: 83868

European-Finnish (FIN) AF: 0.741 AC: 39406 AN: 53156

Middle Eastern (MID) AF: 0.763 AC: 4376 AN: 5732

European-Non Finnish (NFE) AF: 0.700 AC: 768553 AN: 1097570

Other (OTH) AF: 0.755 AC: 45060 AN: 59646

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

African (AFR) AF: 0.877 AC: 36436 AN: 41530

American (AMR) AF: 0.816 AC: 12485 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2551 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5174 AN: 5188

South Asian (SAS) AF: 0.875 AC: 4213 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7929 AN: 10564

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48055 AN: 67994

Other (OTH) AF: 0.793 AC: 1676 AN: 2114

Alfa AF: 0.731 Hom.: 127518

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 v4.9

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
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
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N
PhyloP100		5.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.3	N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.23
MPC		0.049
ClinPred		0.0067	T
GERP RS		5.1
Varity_R		0.057
gMVP		0.39
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7719346; hg19: chr5-111530284; COSMIC: COSV107221502; COSMIC: COSV107221502;