1-28932802-T-C

Position:

• chr1-28932802-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.-8+18034T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,964 control chromosomes in the GnomAD database, including 17,622 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 0.44 (17622 hom., cov: 31)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-8+18034T>C		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.-8+18034T>C		intron_variant		5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67551 AN: 151846 Hom.: 17602 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.445 AC: 67617 AN: 151964 Hom.: 17622 Cov.: 31 AF XY: 0.448 AC XY: 33301 AN XY: 74266

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.441

Alfa AF: 0.374 Hom.: 1997

Bravo AF: 0.473

Asia WGS AF: 0.691 AC: 2399 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.31

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: rs150089; hg19: chr1-29259314; COSMIC: COSV58043242;