2-62826127-G-A

Variant names:

• chr2-62826127-G-A
• rs1365903672
• NM_001142616.3:c.353G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142616.3(EHBP1):​c.353G>A​(p.Ser118Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,391,842 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. S118T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• 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]

ENSG00000226605 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06714022).

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.353G>A	p.Ser118Asn	missense	Exon 6 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.353G>A	p.Ser118Asn	missense	Exon 6 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.353G>A	p.Ser118Asn	missense	Exon 6 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.353G>A	p.Ser118Asn	missense	Exon 6 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.353G>A	p.Ser118Asn	missense	Exon 6 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.353G>A	p.Ser118Asn	missense	Exon 5 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1391842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691076

African (AFR) AF: 0.00 AC: 0 AN: 30320

American (AMR) AF: 0.00 AC: 0 AN: 36858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24224

East Asian (EAS) AF: 0.00 AC: 0 AN: 35626

South Asian (SAS) AF: 0.00 AC: 0 AN: 73110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078010

Other (OTH) AF: 0.00 AC: 0 AN: 56868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		3.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.063
Sift	Benign	0.80	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.29
MutPred		0.13		Loss of phosphorylation at S118 (P = 0.0468)
MVP		0.21
MPC		0.095
ClinPred		0.86	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.091
Mutation Taster		=77/23	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: rs1365903672; hg19: chr2-63053262;