chr2-62826120-A-G

Variant names:

• chr2-62826120-A-G
• NM_001142616.3:c.346A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142616.3(EHBP1):​c.346A>G​(p.Thr116Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,382,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000022 (0 hom.)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

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]

ENSG00000226605 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31531844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.346A>G	p.Thr116Ala	missense_variant	Exon 6 of 23	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.346A>G	p.Thr116Ala	missense_variant	Exon 6 of 23	1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1382522 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 685804

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: 0.0000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

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	0.12
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	.;.;T;.;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	.;T;D;T;D;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.16	N;.;.;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.34	T;T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;T;T;T
Polyphen		1.0	D;.;.;D;P;D
Vest4		0.66
MutPred		0.11		Loss of glycosylation at T116 (P = 0.0322);.;Loss of glycosylation at T116 (P = 0.0322);Loss of glycosylation at T116 (P = 0.0322);Loss of glycosylation at T116 (P = 0.0322);Loss of glycosylation at T116 (P = 0.0322);
MVP		0.51
MPC		0.49
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-63053255;