rs203278

chr1-28915685-T-Cchr1-28915685-T-G

Variant summary

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

The NM_001376013.1(EPB41):c.-8+917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 148,302 control chromosomes in the GnomAD database, including 17,577 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 0.46 (17577 hom., cov: 24)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

Genes affected

EPB41 (HGNC:3377): (erythrocyte membrane protein band 4.1) The protein encoded by this gene, together with spectrin and actin, constitute the red cell membrane cytoskeletal network. This complex plays a critical role in erythrocyte shape and deformability. Mutations in this gene are associated with type 1 elliptocytosis (EL1). Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41	NM_001376013.1	c.-8+917T>C		intron_variant		ENST00000343067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41	ENST00000343067.9	c.-8+917T>C		intron_variant		5	NM_001376013.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 67530 AN: 148190 Hom.: 17562 Cov.: 24

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.456 AC: 67586 AN: 148302 Hom.: 17577 Cov.: 24 AF XY: 0.458 AC XY: 32993 AN XY: 72066

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.453

Alfa AF: 0.338 Hom.: 1589

Bravo AF: 0.485

Asia WGS AF: 0.695 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	13
Dann	Benign	0.82

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: rs203278; hg19: chr1-29242197; COSMIC: COSV58043137;