1-28896865-C-T

Variant names:

• chr1-28896865-C-T
• rs10915207
• ENST00000347529.7:c.-8+9655C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000347529.7(EPB41):​c.-8+9655C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,938 control chromosomes in the GnomAD database, including 20,188 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 0.49 (20188 hom., cov: 31)
• Consequence: EPB41 ENST00000347529.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000347529.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	NM_001166005.2		c.-8+9655C>T		intron	N/A	NP_001159477.1
	EPB41	NM_203343.3		c.-8+9655C>T		intron	N/A	NP_976218.1
	EPB41	NM_001376022.1		c.-618+9655C>T		intron	N/A	NP_001362951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	ENST00000347529.7	TSL:1	c.-8+9655C>T		intron	N/A	ENSP00000290100.6
	EPB41	ENST00000373800.7	TSL:1	c.-698+9655C>T		intron	N/A	ENSP00000362906.3
	EPB41	ENST00000373798.5	TSL:5	c.-8+3028C>T		intron	N/A	ENSP00000362904.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73891 AN: 151822 Hom.: 20179 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.486 AC: 73916 AN: 151938 Hom.: 20188 Cov.: 31 AF XY: 0.501 AC XY: 37196 AN XY: 74248

African (AFR) AF: 0.237 AC: 9833 AN: 41446

American (AMR) AF: 0.629 AC: 9594 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4046 AN: 5150

South Asian (SAS) AF: 0.673 AC: 3244 AN: 4820

European-Finnish (FIN) AF: 0.634 AC: 6680 AN: 10534

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37191 AN: 67940

Other (OTH) AF: 0.487 AC: 1029 AN: 2112

Alfa AF: 0.528 Hom.: 28818

Bravo AF: 0.474

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.39
PhyloP100		-0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10915207; hg19: chr1-29223377;