chr3-55529316-T-C

Variant names:

• chr3-55529316-T-C
• rs1875110
• NM_015576.3:c.*40-18040A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015576.3(ERC2):​c.*40-18040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 152,332 control chromosomes in the GnomAD database, including 95 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 0.031 (95 hom., cov: 33)
• Consequence: ERC2 NM_015576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 3 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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0307 (4669/152332) while in subpopulation NFE AF = 0.0484 (3290/68024). AF 95% confidence interval is 0.047. There are 95 homozygotes in GnomAd4. There are 2188 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4669 AD gene.

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.*40-18040A>G		intron	N/A	NP_056391.1	O15083
	ERC2	NR_132749.2		n.3461-18040A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC2	ENST00000288221.11	TSL:1 MANE Select	c.*40-18040A>G		intron	N/A	ENSP00000288221.6	O15083
	ERC2	ENST00000460849.5	TSL:1	n.*227-18040A>G		intron	N/A	ENSP00000417445.1	O15083
	ERC2	ENST00000484530.5	TSL:1	n.552-18040A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4668 AN: 152214 Hom.: 95 Cov.: 33

Gnomad AFR AF: 0.00869

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0307 AC: 4669 AN: 152332 Hom.: 95 Cov.: 33 AF XY: 0.0294 AC XY: 2188 AN XY: 74496

African (AFR) AF: 0.00866 AC: 360 AN: 41572

American (AMR) AF: 0.0210 AC: 321 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0273 AC: 132 AN: 4830

European-Finnish (FIN) AF: 0.0292 AC: 310 AN: 10626

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0484 AC: 3290 AN: 68024

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0283 Hom.: 26

Bravo AF: 0.0284

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

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: rs1875110; hg19: chr3-55563344;