rs2985334

Positions:

• chr1-29018515-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001376013.1(EPB41):​c.1124+73T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,450,496 control chromosomes in the GnomAD database, including 401,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47139 hom., cov: 31)
  • Exomes 𝑓: 0.74 (354351 hom.)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.587

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-29018515-T-G is Benign according to our data. Variant chr1-29018515-T-G is described in ClinVar as [Benign]. Clinvar id is 1264148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-29018515-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.1124+73T>G		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.1124+73T>G		intron_variant		5	NM_001376013.1	ENSP00000345259

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119040 AN: 151968 Hom.: 47099 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.774

GnomAD4 exome AF: 0.736 AC: 955149 AN: 1298410 Hom.: 354351 AF XY: 0.738 AC XY: 482681 AN XY: 654060

Gnomad4 AFR exome AF: 0.874

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.941

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.783 AC: 119133 AN: 152086 Hom.: 47139 Cov.: 31 AF XY: 0.793 AC XY: 58940 AN XY: 74326

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.776

Alfa AF: 0.721 Hom.: 65352

Bravo AF: 0.787

Asia WGS AF: 0.906 AC: 3151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.69
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: rs2985334; hg19: chr1-29345027; COSMIC: COSV58042785;