dbSNP rs11719646: ERC2:c.657+688T>C (chr3-56433663-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015576.3(ERC2):c.657+688T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,344 control chromosomes in the GnomAD database, including 9,834 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 9830 hom., cov: 33)

Exomes 𝑓: 0.24 ( 4 hom. )

Consequence

ERC2
NM_015576.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.127

Publications

4 publications found

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]

ERC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERC2	NM_015576.3 link	c.657+688T>C		intron_variant	Intron 2 of 17	ENST00000288221.11	NP_056391.1	O15083

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ERC2	ENST00000288221.11 link	c.657+688T>C	intron_variant	Intron 2 of 17	1	NM_015576.3	ENSP00000288221.6	O15083
ERC2	ENST00000460849.5 link	n.657+688T>C	intron_variant	Intron 2 of 18	1		ENSP00000417445.1	O15083
ERC2	ENST00000492584.3 link	c.657+688T>C	intron_variant	Intron 2 of 17	5		ENSP00000417280.3	H7C4G9
ERC2	ENST00000477381.1 link	n.*126T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54101

AN:

152044

Hom.:

9822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.377

GnomAD4 exome

AF:

0.242

AC:

AN:

182

Hom.:

AF XY:

0.198

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.143

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

152

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.356

AC:

54133

AN:

152162

Hom.:

9830

Cov.:

AF XY:

0.349

AC XY:

25990

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.376

AC:

15611

AN:

41490

American (AMR)

AF:

0.279

AC:

4266

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.482

AC:

1672

AN:

3470

East Asian (EAS)

AF:

0.227

AC:

1176

AN:

5184

South Asian (SAS)

AF:

0.156

AC:

750

AN:

4814

European-Finnish (FIN)

AF:

0.381

AC:

4033

AN:

10598

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25399

AN:

67996

Other (OTH)

AF:

0.375

AC:

789

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1815

3629

5444

7258

9073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.365

Hom.:

35254

Bravo

AF:

0.351

Asia WGS

AF:

0.222

AC:

773

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

(source)

DANN

Benign

0.71

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over