rs149177405

Variant names:

• chr2-62707286-C-A
• rs149177405
• NM_001142616.3:c.95C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-62707286-C-A
• chr2-62707286-C-G
• chr2-62707286-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001142616.3(EHBP1):​c.95C>A​(p.Thr32Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T32M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.85
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

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.95C>A	p.Thr32Lys	missense	Exon 2 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.95C>A	p.Thr32Lys	missense	Exon 2 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.95C>A	p.Thr32Lys	missense	Exon 2 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.95C>A	p.Thr32Lys	missense	Exon 2 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.95C>A	p.Thr32Lys	missense	Exon 2 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.95C>A	p.Thr32Lys	missense	Exon 1 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460786 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726794

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111036

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.44		Gain of methylation at T32 (P = 0.0047)
MVP		0.44
MPC		0.57
ClinPred		1.0	D
GERP RS		5.0
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.73
gMVP		0.69
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs149177405; hg19: chr2-62934421;