rs2018650

Positions:

• chr2-63045589-T-C

Variant summary

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

The NM_001142616.3(EHBP1):​c.*89T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,112,730 control chromosomes in the GnomAD database, including 10,448 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 0.11 (1281 hom., cov: 32)
  • Exomes 𝑓: 0.13 (9167 hom.)
• Consequence: EHBP1 NM_001142616.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

Genes affected

EHBP1 (HGNC:29144): (EH domain binding protein 1) This gene encodes an Eps15 homology domain binding protein. The encoded protein may play a role in endocytic trafficking. A single nucleotide polymorphism in this gene is associated with an aggressive form of prostate cancer. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

EHBP1-AS1 (HGNC:55766): (EHBP1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.*89T>C		3_prime_UTR_variant	23/23	ENST00000431489.6	NP_001136088.1
EHBP1-AS1	NR_033389.1	n.408-146A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.*89T>C		3_prime_UTR_variant	23/23	1	NM_001142616.3	ENSP00000403783	A1
EHBP1-AS1	ENST00000650490.1	n.387+893A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17266 AN: 152128 Hom.: 1284 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.130 AC: 124935 AN: 960484 Hom.: 9167 Cov.: 12 AF XY: 0.132 AC XY: 64175 AN XY: 487706

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.113 AC: 17261 AN: 152246 Hom.: 1281 Cov.: 32 AF XY: 0.118 AC XY: 8760 AN XY: 74438

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.135

Alfa AF: 0.132 Hom.: 1888

Bravo AF: 0.115

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.8
DANN	Benign	0.66

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: rs2018650; hg19: chr2-63272724; COSMIC: COSV50417350; COSMIC: COSV50417350;