1-29004677-T-G

Variant names:

• chr1-29004677-T-G
• rs10429865
• NM_001376013.1:c.787-7188T>G

Variant summary

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

The NM_001376013.1(EPB41):​c.787-7188T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,086 control chromosomes in the GnomAD database, including 8,975 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 (8975 hom., cov: 32)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.787-7188T>G		intron	N/A	NP_001362942.1	P11171-1
	EPB41	NM_001166005.2		c.787-7188T>G		intron	N/A	NP_001159477.1	P11171-1
	EPB41	NM_001376014.1		c.787-7188T>G		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.787-7188T>G		intron	N/A	ENSP00000345259.4	P11171-1
	EPB41	ENST00000349460.9	TSL:1	c.787-7188T>G		intron	N/A	ENSP00000317597.8	A0A2U3TZH6
	EPB41	ENST00000347529.7	TSL:1	c.682-7188T>G		intron	N/A	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47324 AN: 151968 Hom.: 8970 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.311 AC: 47344 AN: 152086 Hom.: 8975 Cov.: 32 AF XY: 0.318 AC XY: 23654 AN XY: 74316

African (AFR) AF: 0.114 AC: 4745 AN: 41524

American (AMR) AF: 0.340 AC: 5198 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5178

South Asian (SAS) AF: 0.323 AC: 1552 AN: 4808

European-Finnish (FIN) AF: 0.502 AC: 5283 AN: 10526

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27741 AN: 67992

Other (OTH) AF: 0.316 AC: 667 AN: 2110

Alfa AF: 0.359 Hom.: 13638

Bravo AF: 0.285

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		-0.24
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: rs10429865; hg19: chr1-29331189;