rs34474391

chr1-28981929-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt
EPB41	NM_001376013.1	c.-7-5502T>C		intron_variant		ENST00000343067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41	ENST00000343067.9	c.-7-5502T>C		intron_variant		5	NM_001376013.1

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

Gnomad4 AFR AF: 0.0930

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.0722

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.310

Alfa AF: 0.361 Hom.: 1371

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

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: rs34474391; hg19: chr1-29308441;