chr1-28981929-T-C

Variant names:

• chr1-28981929-T-C
• rs34474391
• NM_001376013.1:c.-7-5502T>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.-7-5502T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,340 control chromosomes in the GnomAD database, including 8,775 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 0.30 (8775 hom., cov: 29)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• 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=-0.91).
• 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 rank	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-7-5502T>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.-7-5502T>C		intron_variant	Intron 1 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46026 AN: 151226 Hom.: 8770 Cov.: 29

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.304 AC: 46036 AN: 151340 Hom.: 8775 Cov.: 29 AF XY: 0.311 AC XY: 22985 AN XY: 73928

African (AFR) AF: 0.0930 AC: 3851 AN: 41412

American (AMR) AF: 0.338 AC: 5132 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5182

South Asian (SAS) AF: 0.321 AC: 1534 AN: 4778

European-Finnish (FIN) AF: 0.496 AC: 5070 AN: 10226

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27636 AN: 67784

Other (OTH) AF: 0.310 AC: 655 AN: 2110

Alfa AF: 0.352 Hom.: 1382

Bravo AF: 0.278

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.44
PhyloP100		0.59
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: rs34474391; hg19: chr1-29308441;