chr2-62993545-C-G

Variant names:

• chr2-62993545-C-G
• rs150215775
• NM_001142616.3:c.2749C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BS2_Supporting

The NM_001142616.3(EHBP1):​c.2749C>G​(p.Leu917Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,594,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L917P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.34
• Publications: 6 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011664897).
• BP6: Variant 2-62993545-C-G is Benign according to our data. Variant chr2-62993545-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3053880.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 125 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.2749C>G	p.Leu917Val	missense	Exon 17 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.2962C>G	p.Leu988Val	missense	Exon 19 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.2962C>G	p.Leu988Val	missense	Exon 19 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.2749C>G	p.Leu917Val	missense	Exon 17 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.2962C>G	p.Leu988Val	missense	Exon 19 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.2857C>G	p.Leu953Val	missense	Exon 17 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes AF: 0.000823 AC: 125 AN: 151914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00101 AC: 250 AN: 247598 AF XY: 0.00108

Gnomad AFR exome AF: 0.000311

Gnomad AMR exome AF: 0.000509

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00155

Gnomad OTH exome AF: 0.000669

GnomAD4 exome AF: 0.00124 AC: 1788 AN: 1442228 Hom.: 1 Cov.: 30 AF XY: 0.00125 AC XY: 899 AN XY: 717576

African (AFR) AF: 0.000211 AC: 7 AN: 33110

American (AMR) AF: 0.000498 AC: 22 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.000314 AC: 8 AN: 25478

East Asian (EAS) AF: 0.00 AC: 0 AN: 39354

South Asian (SAS) AF: 0.00195 AC: 162 AN: 83076

European-Finnish (FIN) AF: 0.000285 AC: 15 AN: 52620

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5666

European-Non Finnish (NFE) AF: 0.00138 AC: 1522 AN: 1099456

Other (OTH) AF: 0.000826 AC: 49 AN: 59306

GnomAD4 genome AF: 0.000822 AC: 125 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.000781 AC XY: 58 AN XY: 74310

African (AFR) AF: 0.000241 AC: 10 AN: 41500

American (AMR) AF: 0.000393 AC: 6 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4816

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.000725

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000980 AC: 119

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
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	0.51	T
Polyphen		0.33	B
Vest4		0.14
MVP		0.43
MPC		0.10
ClinPred		0.028	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.23
Mutation Taster		=92/8	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: rs150215775; hg19: chr2-63220680; COSMIC: COSV99066857;