5-112275765-A-T

Variant names:

• chr5-112275765-A-T
• rs1464765
• NM_022140.5:c.257-361T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.257-361T>A		intron_variant	Intron 3 of 22	ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.257-361T>A		intron_variant	Intron 3 of 22	1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000305368.8	n.531-361T>A		intron_variant	Intron 3 of 5	1
EPB41L4A	ENST00000512395.5	n.220-361T>A		intron_variant	Intron 3 of 6	4
EPB41L4A	ENST00000514203.1	n.70-361T>A		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.475 AC: 19554 AN: 41152

American (AMR) AF: 0.420 AC: 6344 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1153 AN: 3406

East Asian (EAS) AF: 0.338 AC: 1736 AN: 5134

South Asian (SAS) AF: 0.215 AC: 1015 AN: 4722

European-Finnish (FIN) AF: 0.325 AC: 3238 AN: 9960

Middle Eastern (MID) AF: 0.372 AC: 108 AN: 290

European-Non Finnish (NFE) AF: 0.427 AC: 28623 AN: 67010

Other (OTH) AF: 0.417 AC: 859 AN: 2058

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
PhyloP100		-0.051
Mutation Taster		=100/0	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: rs1464765; hg19: chr5-111611462; COSMIC: COSV99814308;