5-112287016-C-T

Position:

• chr5-112287016-C-T

Variant summary

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

The NM_022140.5(EPB41L4A):​c.205-6693G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,134 control chromosomes in the GnomAD database, including 2,394 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 0.17 (2394 hom., cov: 32)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5	c.205-6693G>A		intron_variant		ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.205-6693G>A		intron_variant		1	NM_022140.5	P1
EPB41L4A	ENST00000305368.8	n.479-6693G>A		intron_variant, non_coding_transcript_variant		1
EPB41L4A	ENST00000512395.5	n.168-6693G>A		intron_variant, non_coding_transcript_variant		4
EPB41L4A	ENST00000514203.1	n.18-6693G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25852 AN: 152016 Hom.: 2391 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.170 AC: 25869 AN: 152134 Hom.: 2394 Cov.: 32 AF XY: 0.172 AC XY: 12774 AN XY: 74378

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.179

Alfa AF: 0.155 Hom.: 1869

Bravo AF: 0.177

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.78
DANN	Benign	0.78

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: rs12657885; hg19: chr5-111622713;