rs157231

Positions:

• chr1-28902106-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EPB41	NM_001166005.2	c.-8+14896G>A		intron_variant			NP_001159477.1
EPB41	NM_001166007.2	c.-618+14896G>A		intron_variant			NP_001159479.1
EPB41	NM_001376022.1	c.-618+14896G>A		intron_variant			NP_001362951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000347529.7	c.-8+14896G>A		intron_variant		1		ENSP00000290100
EPB41	ENST00000373800.7	c.-698+14896G>A		intron_variant		1		ENSP00000362906
EPB41	ENST00000373798.5	c.-8+8269G>A		intron_variant		5		ENSP00000362904

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

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.0707

Gnomad4 ASJ exome AF: 0.0913

Gnomad4 EAS exome AF: 0.000905

Gnomad4 SAS exome AF: 0.0207

Gnomad4 FIN exome AF: 0.0480

Gnomad4 NFE exome AF: 0.0791

Gnomad4 OTH exome AF: 0.0829

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.120

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs157231; hg19: chr1-29228618;