rs721048

Positions:

• chr2-62904596-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_001142616.3(EHBP1):​c.1185+30064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,112 control chromosomes in the GnomAD database, including 1,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.13 (1698 hom., cov: 31)
• Consequence: EHBP1 NM_001142616.3 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.575

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 2-62904596-G-A is Pathogenic according to our data. Variant chr2-62904596-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1364.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AMR) 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.1185+30064G>A		intron_variant		ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.1185+30064G>A		intron_variant		1	NM_001142616.3	ENSP00000403783	A1
EHBP1	ENST00000263991.9	c.1290+30064G>A		intron_variant		1		ENSP00000263991	P3
EHBP1	ENST00000405289.5	c.1185+30064G>A		intron_variant		1		ENSP00000385524	A1
EHBP1	ENST00000405015.7	c.1185+30064G>A		intron_variant		2		ENSP00000384143	A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20219 AN: 151994 Hom.: 1697 Cov.: 31

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.133 AC: 20208 AN: 152112 Hom.: 1698 Cov.: 31 AF XY: 0.133 AC XY: 9868 AN XY: 74366

Gnomad4 AFR AF: 0.0365

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.160

Alfa AF: 0.173 Hom.: 2478

Bravo AF: 0.132

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer, hereditary, 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.90

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: rs721048; hg19: chr2-63131731; COSMIC: COSV50416374;