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 ENST00000263991.9(EHBP1):​c.1290+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 ENST00000263991.9 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263991.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	NM_001142616.3	MANE Select	c.1185+30064G>A		intron	N/A	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.1290+30064G>A		intron	N/A	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.1290+30064G>A		intron	N/A	NP_001341142.1	Q8NDI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHBP1	ENST00000431489.6	TSL:1 MANE Select	c.1185+30064G>A		intron	N/A	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.1290+30064G>A		intron	N/A	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.1185+30064G>A		intron	N/A	ENSP00000385524.1	Q8NDI1-2

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	1	-	Prostate cancer, hereditary, 12 (2)
-	1	-	EHBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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;