2-62993526-T-C

Variant names:

• chr2-62993526-T-C
• rs192792364
• NM_001142616.3:c.2734-4T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BS2_Supporting

The NM_001142616.3(EHBP1):​c.2734-4T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.0001817
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.153

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=-0.82).
• 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 rank	MANE	Protein	UniProt
EHBP1	NM_001142616.3	c.2734-4T>C		splice_region_variant, intron_variant	Intron 16 of 22	ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.2734-4T>C		splice_region_variant, intron_variant	Intron 16 of 22	1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 508 AN: 151982 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00258 AC: 625 AN: 242082 AF XY: 0.00244

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 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.: 21 Cov.: 30 AF XY: 0.00411 AC XY: 2916 AN XY: 708736

Gnomad4 AFR exome AF: 0.000612 AC: 20 AN: 32658

Gnomad4 AMR exome AF: 0.00241 AC: 102 AN: 42382

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 24796

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39144

Gnomad4 SAS exome AF: 0.000112 AC: 9 AN: 80126

Gnomad4 FIN exome AF: 0.00206 AC: 107 AN: 51958

Gnomad4 NFE exome AF: 0.00509 AC: 5551 AN: 1090136

Gnomad4 Remaining exome AF: 0.00370 AC: 216 AN: 58404

GnomAD4 genome AF: 0.00334 AC: 508 AN: 152098 Hom.: 2 Cov.: 32 AF XY: 0.00303 AC XY: 225 AN XY: 74356

Gnomad4 AFR AF: 0.000674 AC: 0.000674146 AN: 0.000674146

Gnomad4 AMR AF: 0.00570 AC: 0.00570118 AN: 0.00570118

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.00041511 AN: 0.00041511

Gnomad4 FIN AF: 0.00303 AC: 0.00302973 AN: 0.00302973

Gnomad4 NFE AF: 0.00516 AC: 0.00516389 AN: 0.00516389

Gnomad4 OTH AF: 0.00332 AC: 0.00331754 AN: 0.00331754

Alfa AF: 0.00354 Hom.: 0

Bravo AF: 0.00309

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EHBP1-related disorder Benign:1

May 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs192792364; hg19: chr2-63220661;