rs6702335

Positions:

• chr1-29084738-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376013.1(EPB41):​c.2185-13069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,142 control chromosomes in the GnomAD database, including 8,900 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 0.31 (8900 hom., cov: 32)
• Consequence: EPB41 NM_001376013.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPB41	NM_001376013.1	c.2185-13069A>G		intron_variant		ENST00000343067.9	NP_001362942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPB41	ENST00000343067.9	c.2185-13069A>G		intron_variant		5	NM_001376013.1	ENSP00000345259

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46786 AN: 152024 Hom.: 8894 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.308 AC: 46805 AN: 152142 Hom.: 8900 Cov.: 32 AF XY: 0.315 AC XY: 23396 AN XY: 74362

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.0728

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.313

Alfa AF: 0.352 Hom.: 1740

Bravo AF: 0.281

Asia WGS AF: 0.209 AC: 728 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.51

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: rs6702335; hg19: chr1-29411250;