rs12734106

Variant names:

• chr1-29036314-C-T
• rs12734106
• NM_001376013.1:c.1463+391C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376013.1(EPB41):​c.1463+391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 144,526 control chromosomes in the GnomAD database, including 8,467 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 (8467 hom., cov: 23)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• elliptocytosis 1

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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 rank	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.1463+391C>T		intron_variant	Intron 10 of 20	ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.1463+391C>T		intron_variant	Intron 10 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.306 AC: 44267 AN: 144474 Hom.: 8461 Cov.: 23

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.306 AC: 44277 AN: 144526 Hom.: 8467 Cov.: 23 AF XY: 0.314 AC XY: 21952 AN XY: 69964

African (AFR) AF: 0.0801 AC: 3050 AN: 38078

American (AMR) AF: 0.347 AC: 4887 AN: 14076

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1349 AN: 3448

East Asian (EAS) AF: 0.0748 AC: 357 AN: 4772

South Asian (SAS) AF: 0.324 AC: 1482 AN: 4568

European-Finnish (FIN) AF: 0.508 AC: 4773 AN: 9400

Middle Eastern (MID) AF: 0.331 AC: 88 AN: 266

European-Non Finnish (NFE) AF: 0.408 AC: 27350 AN: 67070

Other (OTH) AF: 0.312 AC: 610 AN: 1956

Alfa AF: 0.354 Hom.: 1201

Bravo AF: 0.273

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.70
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12734106; hg19: chr1-29362826;