3-55529316-T-C

Position:

• chr3-55529316-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4669 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.*40-18040A>G		intron_variant		ENST00000288221.11	NP_056391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERC2	ENST00000288221.11	c.*40-18040A>G		intron_variant		1	NM_015576.3	ENSP00000288221	P1

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

Gnomad4 AFR AF: 0.00866

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0273

Gnomad4 FIN AF: 0.0292

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0326

Alfa AF: 0.0200 Hom.: 7

Bravo AF: 0.0284

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.6
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs1875110; hg19: chr3-55563344;