1-29008768-A-C

Variant names:

• chr1-29008768-A-C
• rs16837840
• NM_001376013.1:c.787-3097A>C

Variant summary

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

The NM_001376013.1(EPB41):​c.787-3097A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,182 control chromosomes in the GnomAD database, including 1,203 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 0.11 (1203 hom., cov: 32)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	NM_001376013.1	MANE Select	c.787-3097A>C		intron	N/A	NP_001362942.1
	EPB41	NM_001166005.2		c.787-3097A>C		intron	N/A	NP_001159477.1
	EPB41	NM_001376014.1		c.787-3097A>C		intron	N/A	NP_001362943.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41	ENST00000343067.9	TSL:5 MANE Select	c.787-3097A>C		intron	N/A	ENSP00000345259.4
	EPB41	ENST00000349460.9	TSL:1	c.787-3097A>C		intron	N/A	ENSP00000317597.8
	EPB41	ENST00000347529.7	TSL:1	c.682-3097A>C		intron	N/A	ENSP00000290100.6

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16487 AN: 152064 Hom.: 1211 Cov.: 32

Gnomad AFR AF: 0.0756

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.108 AC: 16478 AN: 152182 Hom.: 1203 Cov.: 32 AF XY: 0.115 AC XY: 8529 AN XY: 74376

African (AFR) AF: 0.0756 AC: 3140 AN: 41528

American (AMR) AF: 0.145 AC: 2220 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1942 AN: 5166

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1375 AN: 10592

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5979 AN: 68006

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.0944 Hom.: 935

Bravo AF: 0.108

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.57
PhyloP100		-1.1
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: rs16837840; hg19: chr1-29335280;