rs2930833

Variant names:

• chr1-28949506-A-G
• rs2930833
• NM_001376013.1:c.-8+34738A>G

Variant summary

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

The NM_001376013.1(EPB41):​c.-8+34738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,042 control chromosomes in the GnomAD database, including 9,095 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 (9095 hom., cov: 32)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 2 publications found

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]

EPB41 Gene-Disease associations (from GenCC):

• elliptocytosis 1

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-8+34738A>G		intron_variant	Intron 1 of 20	ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.-8+34738A>G		intron_variant	Intron 1 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46435 AN: 151924 Hom.: 9090 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.305 AC: 46445 AN: 152042 Hom.: 9095 Cov.: 32 AF XY: 0.312 AC XY: 23212 AN XY: 74318

African (AFR) AF: 0.0778 AC: 3230 AN: 41500

American (AMR) AF: 0.339 AC: 5180 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3472

East Asian (EAS) AF: 0.0711 AC: 368 AN: 5178

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4820

European-Finnish (FIN) AF: 0.507 AC: 5334 AN: 10518

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28250 AN: 67978

Other (OTH) AF: 0.311 AC: 655 AN: 2108

Alfa AF: 0.354 Hom.: 1410

Bravo AF: 0.277

Asia WGS AF: 0.204 AC: 707 AN: 3462

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	0.52
PhyloP100		0.064
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: rs2930833; hg19: chr1-29276018;