NM_001142616.3:c.567C>T

Variant names:

• chr2-62831091-C-T
• rs764601328
• NM_001142616.3:c.567C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6 BP7 BS2_Supporting

The NM_001142616.3(EHBP1):​c.567C>T​(p.Phe189Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000789 in 1,609,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: EHBP1 NM_001142616.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.60
• Publications: 0 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]

ENSG00000226605 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 2-62831091-C-T is Benign according to our data. Variant chr2-62831091-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3056277.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.6 with no splicing effect.
• BS2: High AC in GnomAd4 at 29 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142616.3. 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.567C>T	p.Phe189Phe	synonymous	Exon 7 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.567C>T	p.Phe189Phe	synonymous	Exon 7 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.567C>T	p.Phe189Phe	synonymous	Exon 7 of 25	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.567C>T	p.Phe189Phe	synonymous	Exon 7 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.567C>T	p.Phe189Phe	synonymous	Exon 7 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.567C>T	p.Phe189Phe	synonymous	Exon 6 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 151808 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000118 AC: 29 AN: 246726 AF XY: 0.000120

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.000149

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000672 AC: 98 AN: 1457366 Hom.: 0 Cov.: 30 AF XY: 0.0000648 AC XY: 47 AN XY: 724948

African (AFR) AF: 0.0000905 AC: 3 AN: 33142

American (AMR) AF: 0.000137 AC: 6 AN: 43686

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26036

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39430

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 85082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5752

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1110642

Other (OTH) AF: 0.0000332 AC: 2 AN: 60220

GnomAD4 genome AF: 0.000191 AC: 29 AN: 151808 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74092

African (AFR) AF: 0.000121 AC: 5 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67978

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.000223 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EHBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=96/4	polymorphism

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: rs764601328; hg19: chr2-63058226; COSMIC: COSV99861400; COSMIC: COSV99861400;