rs2985334

Variant names:

• chr1-29018515-T-G
• rs2985334
• NM_001376013.1:c.1124+73T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-29018515-T-G
• chr1-29018515-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001376013.1(EPB41):​c.1124+73T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,450,496 control chromosomes in the GnomAD database, including 401,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47139 hom., cov: 31)
  • Exomes 𝑓: 0.74 (354351 hom.)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.587
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-29018515-T-G is Benign according to our data. Variant chr1-29018515-T-G is described in ClinVar as Benign. ClinVar VariationId is 1264148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 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.1124+73T>G		intron	N/A	NP_001362942.1	P11171-1
	EPB41	NM_001166005.2		c.1124+73T>G		intron	N/A	NP_001159477.1	P11171-1
	EPB41	NM_001376014.1		c.1124+73T>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.1124+73T>G		intron	N/A	ENSP00000345259.4	P11171-1
	EPB41	ENST00000349460.9	TSL:1	c.1124+73T>G		intron	N/A	ENSP00000317597.8	A0A2U3TZH6
	EPB41	ENST00000347529.7	TSL:1	c.1019+73T>G		intron	N/A	ENSP00000290100.6	P11171-5

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119040 AN: 151968 Hom.: 47099 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.774

GnomAD4 exome AF: 0.736 AC: 955149 AN: 1298410 Hom.: 354351 AF XY: 0.738 AC XY: 482681 AN XY: 654060

African (AFR) AF: 0.874 AC: 26314 AN: 30122

American (AMR) AF: 0.863 AC: 38284 AN: 44376

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 18664 AN: 25138

East Asian (EAS) AF: 0.941 AC: 36676 AN: 38966

South Asian (SAS) AF: 0.836 AC: 68949 AN: 82448

European-Finnish (FIN) AF: 0.789 AC: 41783 AN: 52938

Middle Eastern (MID) AF: 0.709 AC: 3089 AN: 4354

European-Non Finnish (NFE) AF: 0.705 AC: 680529 AN: 965290

Other (OTH) AF: 0.746 AC: 40861 AN: 54778

GnomAD4 genome AF: 0.783 AC: 119133 AN: 152086 Hom.: 47139 Cov.: 31 AF XY: 0.793 AC XY: 58940 AN XY: 74326

African (AFR) AF: 0.870 AC: 36091 AN: 41500

American (AMR) AF: 0.821 AC: 12536 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3470

East Asian (EAS) AF: 0.922 AC: 4779 AN: 5182

South Asian (SAS) AF: 0.852 AC: 4104 AN: 4818

European-Finnish (FIN) AF: 0.801 AC: 8448 AN: 10552

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48156 AN: 67984

Other (OTH) AF: 0.776 AC: 1639 AN: 2112

Alfa AF: 0.733 Hom.: 154631

Bravo AF: 0.787

Asia WGS AF: 0.906 AC: 3151 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		-0.59
PromoterAI		0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs2985334; hg19: chr1-29345027; COSMIC: COSV58042785;