chr2-62747391-G-C

Position:

• chr2-62747391-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BS2_Supporting

The NM_001142616.3(EHBP1):​c.105-4G>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 0.00318 in 1,605,240 control chromosomes in the GnomAD database, including 7 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (6 hom.)
• Consequence: EHBP1 NM_001142616.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001116
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-62747391-G-C is Benign according to our data. Variant chr2-62747391-G-C is described in ClinVar as [Benign]. Clinvar id is 779224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 425 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	c.105-4G>C		splice_region_variant, intron_variant		ENST00000431489.6	NP_001136088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHBP1	ENST00000431489.6	c.105-4G>C		splice_region_variant, intron_variant		1	NM_001142616.3	ENSP00000403783.1

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 425 AN: 151584 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00664

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00296

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00352

Gnomad OTH AF: 0.00529

GnomAD3 exomes AF: 0.00214 AC: 531 AN: 247988 Hom.: 0 AF XY: 0.00195 AC XY: 261 AN XY: 134022

Gnomad AFR exome AF: 0.000811

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.000703

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00399

GnomAD4 exome AF: 0.00322 AC: 4682 AN: 1453538 Hom.: 6 Cov.: 30 AF XY: 0.00310 AC XY: 2240 AN XY: 722878

Gnomad4 AFR exome AF: 0.000605

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.000695

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000237

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00280 AC: 425 AN: 151702 Hom.: 1 Cov.: 32 AF XY: 0.00305 AC XY: 226 AN XY: 74120

Gnomad4 AFR AF: 0.000966

Gnomad4 AMR AF: 0.00663

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00296

Gnomad4 NFE AF: 0.00352

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00289

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.9
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.012
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

Publications

LitVar

Other links and lift over

dbSNP: rs12465326; hg19: chr2-62974526;