rs157231

Variant names:

• chr1-28902106-G-A
• rs157231
• ENST00000347529.7:c.-8+14896G>A

Variant summary

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

The ENST00000347529.7(EPB41):​c.-8+14896G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 923,504 control chromosomes in the GnomAD database, including 4,352 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 0.12 (1572 hom., cov: 32)
  • Exomes 𝑓: 0.081 (2780 hom.)
• Consequence: EPB41 ENST00000347529.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.11
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41	NM_001166005.2	c.-8+14896G>A		intron_variant	Intron 1 of 20		NP_001159477.1
EPB41	NM_203343.3	c.-8+14896G>A		intron_variant	Intron 1 of 16		NP_976218.1
EPB41	NM_001376022.1	c.-618+14896G>A		intron_variant	Intron 1 of 20		NP_001362951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000347529.7	c.-8+14896G>A		intron_variant	Intron 1 of 16	1		ENSP00000290100.6
EPB41	ENST00000373800.7	c.-698+14896G>A		intron_variant	Intron 1 of 18	1		ENSP00000362906.3
EPB41	ENST00000373798.5	c.-8+8269G>A		intron_variant	Intron 1 of 20	5		ENSP00000362904.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18607 AN: 152066 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0812 AC: 62663 AN: 771320 Hom.: 2780 AF XY: 0.0813 AC XY: 29070 AN XY: 357348

African (AFR) AF: 0.260 AC: 3745 AN: 14416

American (AMR) AF: 0.0707 AC: 66 AN: 934

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 435 AN: 4764

East Asian (EAS) AF: 0.000905 AC: 3 AN: 3314

South Asian (SAS) AF: 0.0207 AC: 312 AN: 15088

European-Finnish (FIN) AF: 0.0480 AC: 12 AN: 250

Middle Eastern (MID) AF: 0.112 AC: 169 AN: 1510

European-Non Finnish (NFE) AF: 0.0791 AC: 55834 AN: 705874

Other (OTH) AF: 0.0829 AC: 2087 AN: 25170

GnomAD4 genome AF: 0.122 AC: 18624 AN: 152184 Hom.: 1572 Cov.: 32 AF XY: 0.118 AC XY: 8760 AN XY: 74410

African (AFR) AF: 0.247 AC: 10244 AN: 41470

American (AMR) AF: 0.0804 AC: 1231 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.0214 AC: 103 AN: 4822

European-Finnish (FIN) AF: 0.0677 AC: 717 AN: 10594

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.0820 AC: 5579 AN: 68018

Other (OTH) AF: 0.120 AC: 254 AN: 2112

Alfa AF: 0.0934 Hom.: 300

Bravo AF: 0.131

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.037
DANN	Benign	0.50
PhyloP100		-4.1
Mutation Taster		=99/1	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: rs157231; hg19: chr1-29228618;