NM_001376013.1:c.-7-17476T>C

Variant names:

• chr1-28969955-T-C
• rs2985322
• NM_001376013.1:c.-7-17476T>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.-7-17476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,036 control chromosomes in the GnomAD database, including 17,246 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 (17246 hom., cov: 31)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-7-17476T>C		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.-7-17476T>C		intron_variant	Intron 1 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67009 AN: 151918 Hom.: 17231 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.441 AC: 67068 AN: 152036 Hom.: 17246 Cov.: 31 AF XY: 0.444 AC XY: 33024 AN XY: 74312

African (AFR) AF: 0.665 AC: 27558 AN: 41446

American (AMR) AF: 0.472 AC: 7207 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1250 AN: 3464

East Asian (EAS) AF: 0.851 AC: 4415 AN: 5186

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4816

European-Finnish (FIN) AF: 0.290 AC: 3060 AN: 10568

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19785 AN: 67972

Other (OTH) AF: 0.438 AC: 926 AN: 2112

Alfa AF: 0.311 Hom.: 1763

Bravo AF: 0.469

Asia WGS AF: 0.692 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.72
PhyloP100		0.040
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: rs2985322; hg19: chr1-29296467; COSMIC: COSV58043499;