3-55790384-T-C

Variant names:

• chr3-55790384-T-C
• rs4572738
• NM_015576.3:c.2565-55466A>G

Variant summary

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

The NM_015576.3(ERC2):​c.2565-55466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,968 control chromosomes in the GnomAD database, including 9,948 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 0.33 (9948 hom., cov: 32)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 7 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 = 0.544 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	NM_015576.3	MANE Select	c.2565-55466A>G		intron	N/A	NP_056391.1
	ERC2	NR_132749.2		n.2925-55466A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.2565-55466A>G		intron	N/A	ENSP00000288221.6
	ERC2	ENST00000460849.5	TSL:1	n.2565-55466A>G		intron	N/A	ENSP00000417445.1
	ERC2	ENST00000492584.3	TSL:5	c.2589-55466A>G		intron	N/A	ENSP00000417280.3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50300 AN: 151850 Hom.: 9918 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.332 AC: 50379 AN: 151968 Hom.: 9948 Cov.: 32 AF XY: 0.326 AC XY: 24244 AN XY: 74300

African (AFR) AF: 0.550 AC: 22753 AN: 41404

American (AMR) AF: 0.292 AC: 4455 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1478 AN: 5156

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1629 AN: 10598

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16401 AN: 67950

Other (OTH) AF: 0.340 AC: 717 AN: 2108

Alfa AF: 0.267 Hom.: 9596

Bravo AF: 0.355

Asia WGS AF: 0.337 AC: 1178 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	0.055
DANN	Benign	0.37
PhyloP100		-2.7
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: rs4572738; hg19: chr3-55824412;