chr5-112287016-C-T

Variant names:

• chr5-112287016-C-T
• rs12657885
• NM_022140.5:c.205-6693G>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.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
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022140.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4A	NM_022140.5	MANE Select	c.205-6693G>A		intron	N/A	NP_071423.4
	EPB41L4A	NM_001347887.2		c.205-6693G>A		intron	N/A	NP_001334816.1
	EPB41L4A	NM_001347888.2		c.205-6693G>A		intron	N/A	NP_001334817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L4A	ENST00000261486.6	TSL:1 MANE Select	c.205-6693G>A		intron	N/A	ENSP00000261486.5
	EPB41L4A	ENST00000305368.8	TSL:1	n.479-6693G>A		intron	N/A
	EPB41L4A	ENST00000512395.5	TSL:4	n.168-6693G>A		intron	N/A

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

African (AFR) AF: 0.162 AC: 6711 AN: 41504

American (AMR) AF: 0.208 AC: 3185 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5168

South Asian (SAS) AF: 0.188 AC: 903 AN: 4808

European-Finnish (FIN) AF: 0.161 AC: 1701 AN: 10598

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10513 AN: 67986

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.161 Hom.: 3410

Bravo AF: 0.177

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.78
DANN	Benign	0.78
PhyloP100		-0.90
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: rs12657885; hg19: chr5-111622713;