3-56388878-C-G

Variant names:

• chr3-56388878-C-G
• rs4974210
• NM_015576.3:c.657+45473G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015576.3(ERC2):​c.657+45473G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,956 control chromosomes in the GnomAD database, including 8,745 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 0.34 (8745 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	NM_015576.3	MANE Select	c.657+45473G>C		intron	N/A	NP_056391.1	O15083
	ERC2	NR_132749.2		n.1017+45473G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.657+45473G>C		intron	N/A	ENSP00000288221.6	O15083
	ERC2	ENST00000460849.5	TSL:1	n.657+45473G>C		intron	N/A	ENSP00000417445.1	O15083
	ERC2	ENST00000940588.1		c.657+45473G>C		intron	N/A	ENSP00000610647.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50914 AN: 151838 Hom.: 8722 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50978 AN: 151956 Hom.: 8745 Cov.: 32 AF XY: 0.335 AC XY: 24869 AN XY: 74236

African (AFR) AF: 0.376 AC: 15572 AN: 41412

American (AMR) AF: 0.343 AC: 5231 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.154 AC: 794 AN: 5168

South Asian (SAS) AF: 0.248 AC: 1194 AN: 4808

European-Finnish (FIN) AF: 0.337 AC: 3559 AN: 10576

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22594 AN: 67960

Other (OTH) AF: 0.326 AC: 687 AN: 2106

Alfa AF: 0.310 Hom.: 890

Bravo AF: 0.338

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4974210; hg19: chr3-56422906;