1-28932802-T-C

Variant names:

• chr1-28932802-T-C
• rs150089
• NM_001376013.1:c.-8+18034T>C

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+18034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,964 control chromosomes in the GnomAD database, including 17,622 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 0.44 (17622 hom., cov: 31)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 7 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: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300997 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376013.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	NM_001376013.1	MANE Select	c.-8+18034T>C		intron	N/A	NP_001362942.1	P11171-1
	EPB41	NM_001166005.2		c.-8+45592T>C		intron	N/A	NP_001159477.1	P11171-1
	EPB41	NM_001376014.1		c.-8+18034T>C		intron	N/A	NP_001362943.1	A0A2U3TZH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	ENST00000343067.9	TSL:5 MANE Select	c.-8+18034T>C		intron	N/A	ENSP00000345259.4	P11171-1
	EPB41	ENST00000349460.9	TSL:1	c.-8+18034T>C		intron	N/A	ENSP00000317597.8	A0A2U3TZH6
	EPB41	ENST00000347529.7	TSL:1	c.-8+45592T>C		intron	N/A	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67551 AN: 151846 Hom.: 17602 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.445 AC: 67617 AN: 151964 Hom.: 17622 Cov.: 31 AF XY: 0.448 AC XY: 33301 AN XY: 74266

African (AFR) AF: 0.679 AC: 28126 AN: 41440

American (AMR) AF: 0.474 AC: 7229 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3470

East Asian (EAS) AF: 0.850 AC: 4397 AN: 5170

South Asian (SAS) AF: 0.526 AC: 2534 AN: 4816

European-Finnish (FIN) AF: 0.289 AC: 3035 AN: 10518

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19777 AN: 67970

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.384 Hom.: 2185

Bravo AF: 0.473

Asia WGS AF: 0.691 AC: 2399 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.31
PhyloP100		-0.24
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: rs150089; hg19: chr1-29259314; COSMIC: COSV58043242;