2-62990794-G-T

Variant names:

• chr2-62990794-G-T
• rs1449640150
• NM_001142616.3:c.2687G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142616.3(EHBP1):​c.2687G>T​(p.Ser896Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. S896N) 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: 0.537
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15863937).

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.2687G>T	p.Ser896Ile	missense	Exon 16 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.2900G>T	p.Ser967Ile	missense	Exon 18 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.2900G>T	p.Ser967Ile	missense	Exon 18 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.2687G>T	p.Ser896Ile	missense	Exon 16 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.2900G>T	p.Ser967Ile	missense	Exon 18 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.2795G>T	p.Ser932Ile	missense	Exon 16 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461572 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.54
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.070	T
Polyphen		0.34	B
Vest4		0.21
MutPred		0.17		Loss of glycosylation at S967 (P = 0.0267)
MVP		0.52
MPC		0.12
ClinPred		0.95	D
GERP RS		2.6
Varity_R		0.15
gMVP		0.43
Mutation Taster		=90/10	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: rs1449640150; hg19: chr2-63217929;