3-55790384-T-C

Position:

• chr3-55790384-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERC2	NM_015576.3	c.2565-55466A>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.2565-55466A>G		intron_variant		1	NM_015576.3	ENSP00000288221	P1
ERC2	ENST00000460849.5	c.2565-55466A>G		intron_variant, NMD_transcript_variant		1		ENSP00000417445
ERC2	ENST00000492584.3	c.2589-55466A>G		intron_variant		5		ENSP00000417280

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

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.340

Alfa AF: 0.253 Hom.: 6613

Bravo AF: 0.355

Asia WGS AF: 0.337 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.055
DANN	Benign	0.37

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: rs4572738; hg19: chr3-55824412;