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GeneBe

3-56149037-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015576.3(ERC2):c.1245C>T(p.Arg415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,613,188 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 6 hom. )

Consequence

ERC2
NM_015576.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62
Variant links:
Genes affected
ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-56149037-G-A is Benign according to our data. Variant chr3-56149037-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653906.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.62 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 284 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ERC2NM_015576.3 linkuse as main transcriptc.1245C>T p.Arg415= synonymous_variant 5/18 ENST00000288221.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ERC2ENST00000288221.11 linkuse as main transcriptc.1245C>T p.Arg415= synonymous_variant 5/181 NM_015576.3 P1
ERC2ENST00000460849.5 linkuse as main transcriptc.1245C>T p.Arg415= synonymous_variant, NMD_transcript_variant 5/191
ERC2ENST00000492584.3 linkuse as main transcriptc.1245C>T p.Arg415= synonymous_variant 5/185
ERC2ENST00000484857.2 linkuse as main transcriptn.550C>T non_coding_transcript_exon_variant 2/24

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00187
AC:
284
AN:
151954
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00492
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00260
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00234
AC:
583
AN:
248814
Hom.:
3
AF XY:
0.00230
AC XY:
310
AN XY:
134984
show subpopulations
Gnomad AFR exome
AF:
0.000258
Gnomad AMR exome
AF:
0.00113
Gnomad ASJ exome
AF:
0.00308
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00441
Gnomad NFE exome
AF:
0.00334
Gnomad OTH exome
AF:
0.00298
GnomAD4 exome
AF:
0.00211
AC:
3087
AN:
1461116
Hom.:
6
Cov.:
31
AF XY:
0.00212
AC XY:
1541
AN XY:
726858
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.00125
Gnomad4 ASJ exome
AF:
0.00406
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000650
Gnomad4 FIN exome
AF:
0.00470
Gnomad4 NFE exome
AF:
0.00214
Gnomad4 OTH exome
AF:
0.00273
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00188
AC:
286
AN:
152072
Hom.:
0
Cov.:
33
AF XY:
0.00184
AC XY:
137
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000482
Gnomad4 AMR
AF:
0.00138
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00492
Gnomad4 NFE
AF:
0.00260
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00198
Hom.:
0
Bravo
AF:
0.00162
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00328
EpiControl
AF:
0.00338

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2023ERC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.0
Dann
Benign
0.69

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs186918021; hg19: chr3-56183065; API