5-112275765-A-T

Position:

• chr5-112275765-A-T

Variant summary

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

The NM_022140.5(EPB41L4A):​c.257-361T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 149,740 control chromosomes in the GnomAD database, including 13,422 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13422 hom., cov: 32)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.257-361T>A		intron_variant		ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.257-361T>A		intron_variant		1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000305368.8	n.531-361T>A		intron_variant		1
EPB41L4A	ENST00000512395.5	n.220-361T>A		intron_variant		4
EPB41L4A	ENST00000514203.1	n.70-361T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63074 AN: 149624 Hom.: 13407 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.422 AC: 63137 AN: 149740 Hom.: 13422 Cov.: 32 AF XY: 0.412 AC XY: 30067 AN XY: 73060

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.417

Alfa AF: 0.173 Hom.: 247

Bravo AF: 0.435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
DANN	Benign	0.61

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: rs1464765; hg19: chr5-111611462;