rs35423185

Positions:

• chr1-29053860-C-T

Variant summary

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

The NM_001376013.1(EPB41):​c.1845+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 153,630 control chromosomes in the GnomAD database, including 9,006 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 0.31 (8879 hom., cov: 32)
  • Exomes 𝑓: 0.37 (127 hom.)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.1845+548C>T		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.1845+548C>T		intron_variant		5	NM_001376013.1	ENSP00000345259

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46486 AN: 151882 Hom.: 8872 Cov.: 32

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.367 AC: 596 AN: 1626 Hom.: 127 Cov.: 0 AF XY: 0.367 AC XY: 338 AN XY: 922

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.306 AC: 46504 AN: 152004 Hom.: 8879 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74292

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.0721

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.312

Alfa AF: 0.361 Hom.: 1366

Bravo AF: 0.278

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.65

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: rs35423185; hg19: chr1-29380372;