rs145427390

Variant names:

• chr2-62996726-C-G
• rs145427390
• NM_001142616.3:c.3063C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-62996726-C-G
• chr2-62996726-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BP6_Moderate BP7 BS2_Supporting

The NM_001142616.3(EHBP1):​c.3063C>G​(p.Ala1021Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,612,994 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (1 hom.)
• Consequence: EHBP1 NM_001142616.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.20
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 2-62996726-C-G is Benign according to our data. Variant chr2-62996726-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2650992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.2 with no splicing effect.
• BS2: High AC in GnomAd4 at 80 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.3063C>G	p.Ala1021Ala	synonymous	Exon 19 of 23	NP_001136088.1	Q8NDI1-3
	EHBP1	NM_001354212.1		c.3276C>G	p.Ala1092Ala	synonymous	Exon 21 of 25	NP_001341141.1	Q8NDI1-1
	EHBP1	NM_001354213.1		c.3276C>G	p.Ala1092Ala	synonymous	Exon 21 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.3063C>G	p.Ala1021Ala	synonymous	Exon 19 of 23	ENSP00000403783.1	Q8NDI1-3
	EHBP1	ENST00000263991.9	TSL:1	c.3276C>G	p.Ala1092Ala	synonymous	Exon 21 of 25	ENSP00000263991.5	Q8NDI1-1
	EHBP1	ENST00000405289.5	TSL:1	c.3171C>G	p.Ala1057Ala	synonymous	Exon 19 of 23	ENSP00000385524.1	Q8NDI1-2

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152062 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000487 AC: 122 AN: 250302 AF XY: 0.000495

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00279

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000725

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000427 AC: 624 AN: 1460814 Hom.: 1 Cov.: 31 AF XY: 0.000432 AC XY: 314 AN XY: 726730

African (AFR) AF: 0.0000300 AC: 1 AN: 33388

American (AMR) AF: 0.000157 AC: 7 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86190

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000471 AC: 523 AN: 1111502

Other (OTH) AF: 0.000613 AC: 37 AN: 60320

GnomAD4 genome AF: 0.000526 AC: 80 AN: 152180 Hom.: 1 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74390

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.000197 AC: 3 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68010

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000914 Hom.: 0

Bravo AF: 0.000438

EpiCase AF: 0.000982

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		3.2
Mutation Taster		=100/0	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: rs145427390; hg19: chr2-63223861;