rs140695994

Variant names:

• chr2-62987954-G-C
• rs140695994
• ENST00000263991.9:c.2737G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-62987954-G-C
• chr2-62987954-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015252.5(EHBP1):​c.2737G>C​(p.Asp913His) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EHBP1 NM_015252.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11258322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.2609-2762G>C		intron_variant	Intron 15 of 22	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.2609-2762G>C		intron_variant	Intron 15 of 22	1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247482 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133844

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442686 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 718202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.18	B;B
Vest4		0.38
MutPred		0.12		Gain of helix (P = 0.0854);.;
MVP		0.50
MPC		0.25
ClinPred		0.44	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs140695994; hg19: chr2-63215089;