chr5-112270254-G-A

Position:

• chr5-112270254-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41L4A	NM_022140.5	c.336-3924C>T		intron_variant		ENST00000261486.6	NP_071423.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.336-3924C>T		intron_variant		1	NM_022140.5	ENSP00000261486	P1
EPB41L4A	ENST00000305368.8	n.610-3924C>T		intron_variant, non_coding_transcript_variant		1
EPB41L4A	ENST00000512395.5	n.299-3924C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0670 Hom.: 160

Bravo AF: 0.0630

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.47

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: rs13361927; hg19: chr5-111605951;