rs12039988

Positions:

• chr1-29099321-G-A
• chr1-29099321-G-C
• chr1-29099321-G-T

Variant summary

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

The NM_001376013.1(EPB41):​c.2313+1386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 149,402 control chromosomes in the GnomAD database, including 8,744 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 (8744 hom., cov: 27)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB41	NM_001376013.1	c.2313+1386G>A		intron_variant		ENST00000343067.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB41	ENST00000343067.9	c.2313+1386G>A		intron_variant		5	NM_001376013.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46129 AN: 149320 Hom.: 8739 Cov.: 27

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.309 AC: 46146 AN: 149402 Hom.: 8744 Cov.: 27 AF XY: 0.316 AC XY: 22998 AN XY: 72782

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.315

Alfa AF: 0.352 Hom.: 4348

Bravo AF: 0.280

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.49

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: rs12039988; hg19: chr1-29425833;