Variant 2-62993526-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting

The NM_001142616.3(EHBP1):c.2734-4T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,577,296 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 21 hom. )

Consequence

EHBP1
NM_001142616.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001817

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.153

Variant links:

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 links:

EHBP1-AS1 (HGNC:55766): (EHBP1 antisense RNA 1)

EHBP1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-62993526-T-C is Benign according to our data. Variant chr2-62993526-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038064.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 508 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHBP1	NM_001142616.3 linkuse as main transcript	c.2734-4T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6 linkuse as main transcript	c.2734-4T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001142616.3	ENSP00000403783	A1	Q8NDI1-3
EHBP1-AS1	ENST00000650490.1 linkuse as main transcript	n.572+20033A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00334

AC:

508

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00571

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00258

AC:

625

AN:

242082

Hom.:

AF XY:

0.00244

AC XY:

320

AN XY:

131254

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00201

Gnomad NFE exome

AF:

0.00429

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00422

AC:

6017

AN:

1425198

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

2916

AN XY:

708736

show subpopulations

Gnomad4 AFR exome

AF:

0.000612

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000112

Gnomad4 FIN exome

AF:

0.00206

Gnomad4 NFE exome

AF:

0.00509

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.00334

AC:

508

AN:

152098

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

225

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00570

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.00309

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EHBP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.3

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.042

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over