rs12027267

Positions:

• chr1-29052363-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376013.1(EPB41):​c.1637-741C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,134 control chromosomes in the GnomAD database, including 8,875 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 0.31 (8875 hom., cov: 32)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41	NM_001376013.1	c.1637-741C>A		intron_variant		ENST00000343067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41	ENST00000343067.9	c.1637-741C>A		intron_variant		5	NM_001376013.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46426 AN: 152016 Hom.: 8869 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.305 AC: 46442 AN: 152134 Hom.: 8875 Cov.: 32 AF XY: 0.312 AC XY: 23207 AN XY: 74350

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.310

Alfa AF: 0.361 Hom.: 1391

Bravo AF: 0.278

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.83
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: rs12027267; hg19: chr1-29378875;