2-62747391-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001142616.3(EHBP1):c.105-4G>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 0.00318 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, splice_polypyrimidine_tract, 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]

ACMG classification

Verdict is Benign. Variant got -10 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 GnomAd at 425 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EHBP1	ENST00000431489.6	c.105-4G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001142616.3	A1

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

Invitae

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;