5-112357674-T-C

Position:

• chr5-112357674-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022140.5(EPB41L4A):​c.100-50184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,280 control chromosomes in the GnomAD database, including 140 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 0.034 (140 hom., cov: 33)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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 (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0345 (5253/152280) while in subpopulation NFE AF= 0.0484 (3292/68014). AF 95% confidence interval is 0.047. There are 140 homozygotes in gnomad4. There are 2655 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 140 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.100-50184A>G		intron_variant		ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.100-50184A>G		intron_variant		1	NM_022140.5	ENSP00000261486.5
EPB41L4A	ENST00000305368.8	n.374-50184A>G		intron_variant		1
EPB41L4A	ENST00000512395.5	n.62+35049A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5251 AN: 152162 Hom.: 140 Cov.: 33

Gnomad AFR AF: 0.00758

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0345 AC: 5253 AN: 152280 Hom.: 140 Cov.: 33 AF XY: 0.0357 AC XY: 2655 AN XY: 74462

Gnomad4 AFR AF: 0.00755

Gnomad4 AMR AF: 0.0329

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0449 Hom.: 223

Bravo AF: 0.0288

Asia WGS AF: 0.00924 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.83

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: rs379440; hg19: chr5-111693371;