NM_001142616.3:c.2905A>T

Variant names:

• chr2-62993903-A-T
• rs1170805020
• NM_001142616.3:c.2905A>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.2905A>T​(p.Thr969Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EHBP1 NM_001142616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• 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=0.24062815).

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.2905A>T	p.Thr969Ser	missense	Exon 18 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.3118A>T	p.Thr1040Ser	missense	Exon 20 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.3118A>T	p.Thr1040Ser	missense	Exon 20 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.2905A>T	p.Thr969Ser	missense	Exon 18 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.3118A>T	p.Thr1040Ser	missense	Exon 20 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.3013A>T	p.Thr1005Ser	missense	Exon 18 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151496 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445616 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717414

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.00 AC: 0 AN: 43368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25684

East Asian (EAS) AF: 0.00 AC: 0 AN: 39218

South Asian (SAS) AF: 0.00 AC: 0 AN: 83504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102702

Other (OTH) AF: 0.00 AC: 0 AN: 59740

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151496 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73976

African (AFR) AF: 0.0000242 AC: 1 AN: 41302

American (AMR) AF: 0.000132 AC: 2 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.25
Sift	Benign	0.089	T
Sift4G	Benign	0.68	T
Polyphen		0.97	D
Vest4		0.33
MutPred		0.070		Gain of MoRF binding (P = 0.1364)
MVP		0.62
MPC		0.20
ClinPred		0.89	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.20
Mutation Taster		=78/22	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: rs1170805020; hg19: chr2-63221038;