chr5-112275765-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022140.5(EPB41L4A):​c.257-361T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 149,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149708 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149708 Hom.: 0 Cov.: 32 AF XY: 0.0000274 AC XY: 2 AN XY: 72976

African (AFR) AF: 0.00 AC: 0 AN: 41062

American (AMR) AF: 0.00 AC: 0 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4734

European-Finnish (FIN) AF: 0.000100 AC: 1 AN: 9972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67038

Other (OTH) AF: 0.00 AC: 0 AN: 2038

Alfa AF: 0.00 Hom.: 247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		-0.051

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;