2-62826219-G-T

Variant names:

• chr2-62826219-G-T
• rs191293806
• NM_001142616.3:c.445G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142616.3(EHBP1):​c.445G>T​(p.Ala149Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046912104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.445G>T	p.Ala149Ser	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.445G>T	p.Ala149Ser	missense_variant	Exon 6 of 23	1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.85
DEOGEN2	Benign	0.0072	.;T;T;T;.;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	.;D;D;D;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.047	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N;.;.;.;N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	1.3	N;N;N;N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.56	T;D;T;T;T;T;T
Sift4G	Benign	0.60	T;D;T;T;T;T;T
Polyphen		0.011	B;.;.;.;B;B;B
Vest4		0.28
MutPred		0.23		Gain of disorder (P = 0.0218);.;.;Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);
MVP		0.082
MPC		0.097
ClinPred		0.55	D
GERP RS		4.3
Varity_R		0.089
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs191293806; hg19: chr2-63053354;