rs721048

Variant names:

• chr2-62904596-G-A
• rs721048
• NM_001142616.3:c.1185+30064G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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 Uncertain significance (★★).

• Frequency: Genomes: 𝑓 0.13 (1698 hom., cov: 31)
• Consequence: EHBP1 NM_001142616.3 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts P:1 U:2
• Conservation: PhyloP100: 0.575
• Publications: 147 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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 rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.1185+30064G>A		intron_variant	Intron 10 of 22	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.1185+30064G>A		intron_variant	Intron 10 of 22	1	NM_001142616.3	ENSP00000403783.1
EHBP1	ENST00000263991.9	c.1290+30064G>A		intron_variant	Intron 11 of 24	1		ENSP00000263991.5
EHBP1	ENST00000405289.5	c.1185+30064G>A		intron_variant	Intron 9 of 22	1		ENSP00000385524.1
EHBP1	ENST00000405015.7	c.1185+30064G>A		intron_variant	Intron 10 of 22	2		ENSP00000384143.3

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

African (AFR) AF: 0.0365 AC: 1517 AN: 41510

American (AMR) AF: 0.184 AC: 2821 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3468

East Asian (EAS) AF: 0.0476 AC: 246 AN: 5164

South Asian (SAS) AF: 0.100 AC: 483 AN: 4812

European-Finnish (FIN) AF: 0.155 AC: 1646 AN: 10590

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12415 AN: 67966

Other (OTH) AF: 0.160 AC: 337 AN: 2110

Alfa AF: 0.163 Hom.: 5783

Bravo AF: 0.132

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Prostate cancer, hereditary, 12 Pathogenic:1 Uncertain:1

Dec 18, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2008

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

EHBP1-related disorder Uncertain:1

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.90
PhyloP100		0.57
Mutation Taster		=100/0	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs721048; hg19: chr2-63131731;