1-28987863-C-T

Variant names:

• chr1-28987863-C-T
• NM_001376013.1:c.426C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001376013.1(EPB41):​c.426C>T​(p.Asp142Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB41 NM_001376013.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-28987863-C-T is Benign according to our data. Variant chr1-28987863-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1330438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.574 with no splicing effect.

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.426C>T	p.Asp142Asp	synonymous	Exon 2 of 21	NP_001362942.1	P11171-1
	EPB41	NM_001166005.2		c.426C>T	p.Asp142Asp	synonymous	Exon 2 of 21	NP_001159477.1	P11171-1
	EPB41	NM_001376014.1		c.426C>T	p.Asp142Asp	synonymous	Exon 2 of 20	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.426C>T	p.Asp142Asp	synonymous	Exon 2 of 21	ENSP00000345259.4	P11171-1
	EPB41	ENST00000349460.9	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 2 of 20	ENSP00000317597.8	A0A2U3TZH6
	EPB41	ENST00000347529.7	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 2 of 17	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Elliptocytosis 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.2
DANN	Benign	0.78
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=292/8	polymorphism

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

hg19: chr1-29314375; COSMIC: COSV100548333; COSMIC: COSV100548333;