1-28896865-C-T

Position:

• chr1-28896865-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+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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41	NM_001166005.2	c.-8+9655C>T		intron_variant
EPB41	NM_001166007.2	c.-618+9655C>T		intron_variant
EPB41	NM_001376022.1	c.-618+9655C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41	ENST00000347529.7	c.-8+9655C>T		intron_variant		1
EPB41	ENST00000373800.7	c.-698+9655C>T		intron_variant		1
EPB41	ENST00000373798.5	c.-8+3028C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.487

Alfa AF: 0.538 Hom.: 22798

Bravo AF: 0.474

Asia WGS AF: 0.684 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10915207; hg19: chr1-29223377;