5-112270254-G-A

Variant names:

• chr5-112270254-G-A
• rs13361927
• NM_022140.5:c.336-3924C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022140.5(EPB41L4A):​c.336-3924C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,190 control chromosomes in the GnomAD database, including 385 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 0.066 (385 hom., cov: 32)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 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.336-3924C>T		intron	N/A	NP_071423.4
	EPB41L4A	NM_001347887.2		c.336-3924C>T		intron	N/A	NP_001334816.1
	EPB41L4A	NM_001347888.2		c.336-3924C>T		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.336-3924C>T		intron	N/A	ENSP00000261486.5
	EPB41L4A	ENST00000305368.8	TSL:1	n.610-3924C>T		intron	N/A
	EPB41L4A	ENST00000512395.5	TSL:4	n.299-3924C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10056 AN: 152072 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0575

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

GnomAD4 genome AF: 0.0661 AC: 10064 AN: 152190 Hom.: 385 Cov.: 32 AF XY: 0.0664 AC XY: 4944 AN XY: 74416

African (AFR) AF: 0.0756 AC: 3137 AN: 41504

American (AMR) AF: 0.0524 AC: 802 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3466

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0687 AC: 4672 AN: 68010

Other (OTH) AF: 0.0569 AC: 120 AN: 2110

Alfa AF: 0.0672 Hom.: 185

Bravo AF: 0.0630

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.12
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: rs13361927; hg19: chr5-111605951;