2-62979326-G-C

Variant names:

• chr2-62979326-G-C
• rs747490913
• NM_001142616.3:c.2599G>C

Variant summary

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

The NM_001142616.3(EHBP1):​c.2599G>C​(p.Ala867Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.2599G>C	p.Ala867Pro	missense_variant	Exon 15 of 23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.2599G>C	p.Ala867Pro	missense_variant	Exon 15 of 23	1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250956 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461184 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0069	.;.;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;T;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.0	.;.;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.13	T;T;D;D
Sift4G	Benign	0.30	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.62
MutPred		0.071		.;.;Loss of stability (P = 0.0969);.;
MVP		0.39
MPC		0.16
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.40
gMVP		0.35

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: rs747490913; hg19: chr2-63206461;