chr1-29099321-G-A

Variant names:

• chr1-29099321-G-A
• rs12039988
• NM_001376013.1:c.2313+1386G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376013.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	NM_001376013.1	MANE Select	c.2313+1386G>A		intron	N/A	NP_001362942.1	P11171-1
	EPB41	NM_001166005.2		c.2313+1386G>A		intron	N/A	NP_001159477.1	P11171-1
	EPB41	NM_001376014.1		c.2244+1386G>A		intron	N/A	NP_001362943.1	A0A2U3TZH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	ENST00000343067.9	TSL:5 MANE Select	c.2313+1386G>A		intron	N/A	ENSP00000345259.4	P11171-1
	EPB41	ENST00000349460.9	TSL:1	c.2244+1386G>A		intron	N/A	ENSP00000317597.8	A0A2U3TZH6
	EPB41	ENST00000347529.7	TSL:1	c.2046+1386G>A		intron	N/A	ENSP00000290100.6	P11171-5

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

African (AFR) AF: 0.101 AC: 4114 AN: 40544

American (AMR) AF: 0.344 AC: 5149 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1343 AN: 3452

East Asian (EAS) AF: 0.0738 AC: 368 AN: 4986

South Asian (SAS) AF: 0.323 AC: 1504 AN: 4650

European-Finnish (FIN) AF: 0.507 AC: 5131 AN: 10114

Middle Eastern (MID) AF: 0.309 AC: 89 AN: 288

European-Non Finnish (NFE) AF: 0.407 AC: 27462 AN: 67450

Other (OTH) AF: 0.315 AC: 650 AN: 2062

Alfa AF: 0.354 Hom.: 4973

Bravo AF: 0.280

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.49
PhyloP100		-0.57
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: rs12039988; hg19: chr1-29425833;