rs2018650

Variant names:

• chr2-63045589-T-C
• rs2018650
• ENST00000496857.5:n.1188T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000496857.5(EHBP1):​n.1188T>C variant causes a non coding transcript exon 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 ENST00000496857.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 12 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.*89T>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.*89T>C		3_prime_UTR_variant	Exon 23 of 23	1	NM_001142616.3	ENSP00000403783.1

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

African (AFR) AF: 0.0243 AC: 555 AN: 22806

American (AMR) AF: 0.231 AC: 7354 AN: 31896

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4229 AN: 21124

East Asian (EAS) AF: 0.167 AC: 5586 AN: 33516

South Asian (SAS) AF: 0.162 AC: 10809 AN: 66774

European-Finnish (FIN) AF: 0.151 AC: 7067 AN: 46768

Middle Eastern (MID) AF: 0.193 AC: 909 AN: 4716

European-Non Finnish (NFE) AF: 0.120 AC: 82521 AN: 689388

Other (OTH) AF: 0.136 AC: 5905 AN: 43496

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

African (AFR) AF: 0.0278 AC: 1155 AN: 41554

American (AMR) AF: 0.184 AC: 2814 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3468

East Asian (EAS) AF: 0.189 AC: 983 AN: 5188

South Asian (SAS) AF: 0.155 AC: 748 AN: 4824

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8723 AN: 68016

Other (OTH) AF: 0.135 AC: 286 AN: 2114

Alfa AF: 0.131 Hom.: 2430

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
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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