rs1464766

chr5-112277645-A-Gchr5-112277645-A-T

Variant summary

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

The NM_022140.5(EPB41L4A):c.257-2241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,068 control chromosomes in the GnomAD database, including 27,644 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 0.59 (27644 hom., cov: 31)
• Consequence: EPB41L4A NM_022140.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41L4A	NM_022140.5	c.257-2241T>C		intron_variant		ENST00000261486.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41L4A	ENST00000261486.6	c.257-2241T>C		intron_variant		1	NM_022140.5	P1
EPB41L4A	ENST00000305368.8	n.531-2241T>C		intron_variant, non_coding_transcript_variant		1
EPB41L4A	ENST00000512395.5	n.220-2241T>C		intron_variant, non_coding_transcript_variant		4
EPB41L4A	ENST00000514203.1	n.70-2241T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90092 AN: 151950 Hom.: 27633 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.593 AC: 90145 AN: 152068 Hom.: 27644 Cov.: 31 AF XY: 0.600 AC XY: 44605 AN XY: 74330

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.622

Alfa AF: 0.633 Hom.: 37424

Bravo AF: 0.575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.64

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: rs1464766; hg19: chr5-111613342;