chr1-28971164-T-C

Variant names:

• chr1-28971164-T-C
• rs7546832
• NM_001376013.1:c.-7-16267T>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.-7-16267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 143,264 control chromosomes in the GnomAD database, including 8,091 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 0.30 (8091 hom., cov: 26)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.-7-16267T>C		intron_variant	Intron 1 of 20	ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.-7-16267T>C		intron_variant	Intron 1 of 20	5	NM_001376013.1	ENSP00000345259.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 43263 AN: 143164 Hom.: 8084 Cov.: 26

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.0717

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.302

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.302 AC: 43278 AN: 143264 Hom.: 8091 Cov.: 26 AF XY: 0.305 AC XY: 21011 AN XY: 68830

African (AFR) AF: 0.102 AC: 3991 AN: 39088

American (AMR) AF: 0.325 AC: 4413 AN: 13582

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1335 AN: 3428

East Asian (EAS) AF: 0.0717 AC: 348 AN: 4854

South Asian (SAS) AF: 0.319 AC: 1449 AN: 4536

European-Finnish (FIN) AF: 0.474 AC: 3798 AN: 8020

Middle Eastern (MID) AF: 0.300 AC: 81 AN: 270

European-Non Finnish (NFE) AF: 0.404 AC: 26928 AN: 66608

Other (OTH) AF: 0.307 AC: 609 AN: 1986

Alfa AF: 0.352 Hom.: 1125

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.64
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: rs7546832; hg19: chr1-29297676;