rs4654328

Positions:

• chr1-28903833-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000347529.7(EPB41):​c.-8+16623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,806 control chromosomes in the GnomAD database, including 8,895 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 (8895 hom., cov: 30)
• Consequence: EPB41 ENST00000347529.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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=-0.95).
• 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	Protein	UniProt
EPB41	NM_001166005.2	c.-8+16623C>T		intron_variant			NP_001159477.1
EPB41	NM_001166007.2	c.-618+16623C>T		intron_variant			NP_001159479.1
EPB41	NM_001376022.1	c.-618+16623C>T		intron_variant			NP_001362951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000347529.7	c.-8+16623C>T		intron_variant		1		ENSP00000290100
EPB41	ENST00000373800.7	c.-698+16623C>T		intron_variant		1		ENSP00000362906
EPB41	ENST00000373798.5	c.-8+9996C>T		intron_variant		5		ENSP00000362904

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46677 AN: 151690 Hom.: 8890 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.308 AC: 46697 AN: 151806 Hom.: 8895 Cov.: 30 AF XY: 0.315 AC XY: 23366 AN XY: 74182

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.313

Alfa AF: 0.385 Hom.: 2797

Bravo AF: 0.280

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.59

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: rs4654328; hg19: chr1-29230345;