ENST00000347529.7:c.-8+9655C>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000347529.7(EPB41):​c.-8+9655C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>G		intron	N/A	NP_001159477.1
	EPB41	NM_203343.3		c.-8+9655C>G		intron	N/A	NP_976218.1
	EPB41	NM_001376022.1		c.-618+9655C>G		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>G		intron	N/A	ENSP00000290100.6
	EPB41	ENST00000373800.7	TSL:1	c.-698+9655C>G		intron	N/A	ENSP00000362906.3
	EPB41	ENST00000373798.5	TSL:5	c.-8+3028C>G		intron	N/A	ENSP00000362904.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 28818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.40
PhyloP100		-0.37

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;