1-28987182-C-A

Position:

• chr1-28987182-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001376013.1(EPB41):​c.-7-249C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,128 control chromosomes in the GnomAD database, including 47,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47131 hom., cov: 31)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-28987182-C-A is Benign according to our data. Variant chr1-28987182-C-A is described in ClinVar as [Benign]. Clinvar id is 1290643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-7-249C>A		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.-7-249C>A		intron_variant		5	NM_001376013.1	ENSP00000345259

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118872 AN: 152010 Hom.: 47089 Cov.: 31

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.782 AC: 118967 AN: 152128 Hom.: 47131 Cov.: 31 AF XY: 0.791 AC XY: 58827 AN XY: 74350

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.775

Alfa AF: 0.742 Hom.: 7946

Bravo AF: 0.787

Asia WGS AF: 0.904 AC: 3142 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.74

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: rs2930838; hg19: chr1-29313694;