rs1064125

Positions:

• chr12-1491812-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178040.4(ERC1):​c.*1582A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 232,090 control chromosomes in the GnomAD database, including 10,147 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 0.21 (5127 hom., cov: 32)
  • Exomes 𝑓: 0.28 (5020 hom.)
• Consequence: ERC1 NM_178040.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

Genes affected

ERC1 (HGNC:17072): (ELKS/RAB6-interacting/CAST family member 1) The protein encoded by this gene is a member of a family of RIM-binding proteins. RIMs are active zone proteins that regulate neurotransmitter release. This gene has been found fused to the receptor-type tyrosine kinase gene RET by gene rearrangement due to the translocation t(10;12)(q11;p13) in thyroid papillary carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERC1	NM_178040.4	c.*1582A>T		3_prime_UTR_variant	19/19	ENST00000360905.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERC1	ENST00000360905.9	c.*1582A>T		3_prime_UTR_variant	19/19	1	NM_178040.4

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32624 AN: 152036 Hom.: 5120 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.282 AC: 22574 AN: 79936 Hom.: 5020 Cov.: 0 AF XY: 0.280 AC XY: 10288 AN XY: 36740

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.798

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.215 AC: 32638 AN: 152154 Hom.: 5127 Cov.: 32 AF XY: 0.227 AC XY: 16885 AN XY: 74378

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.177

Alfa AF: 0.229 Hom.: 646

Bravo AF: 0.203

Asia WGS AF: 0.547 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.76
DANN	Benign	0.76

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: rs1064125; hg19: chr12-1600978;