15-43203014-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001114134.2(EPB42):c.1779+101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,432,564 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (827 hom., cov: 31)
  • Exomes 𝑓: 0.0098 (829 hom.)
• Consequence: EPB42 NM_001114134.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.362

Genes affected

EPB42 (HGNC:3381): (erythrocyte membrane protein band 4.2) Erythrocyte membrane protein band 4.2 is an ATP-binding protein which may regulate the association of protein 3 with ankyrin. It probably has a role in erythrocyte shape and mechanical property regulation. Mutations in the EPB42 gene are associated with recessive spherocytic elliptocytosis and recessively transmitted hereditary hemolytic anemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-43203014-T-C is Benign according to our data. Variant chr15-43203014-T-C is described in ClinVar as [Benign]. Clinvar id is 1262595.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-43203014-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPB42	NM_001114134.2	c.1779+101A>G		intron_variant		ENST00000441366.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPB42	ENST00000441366.7	c.1779+101A>G		intron_variant		1	NM_001114134.2	P1
EPB42	ENST00000567019.2	n.1285+101A>G		intron_variant, non_coding_transcript_variant		1
EPB42	ENST00000540029.5	c.1545+101A>G		intron_variant		2
EPB42	ENST00000648595.1	c.1869+101A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9074 AN: 152078 Hom.: 822 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.00976 AC: 12492 AN: 1280368 Hom.: 829 AF XY: 0.00880 AC XY: 5690 AN XY: 646322

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0137

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.00456

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000492

Gnomad4 OTH exome AF: 0.0225

GnomAD4 genome AF: 0.0598 AC: 9106 AN: 152196 Hom.: 827 Cov.: 31 AF XY: 0.0578 AC XY: 4298 AN XY: 74420

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0119 Hom.: 214

Bravo AF: 0.0679

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.1
Dann	Benign	0.72

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: rs1863601; hg19: chr15-43495212; COSMIC: COSV55751551; COSMIC: COSV55751551;