ENST00000440394.7:n.*1947A>T

Variant names:

• chr12-1491812-A-T
• rs1064125
• ENST00000440394.7:n.*1947A>T

Variant summary

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

The ENST00000440394.7(ERC1):​n.*1947A>T variant causes a non coding transcript exon 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 ENST00000440394.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERC1	NM_178040.4	c.*1582A>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000360905.9	NP_829884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERC1	ENST00000360905.9	c.*1582A>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_178040.4	ENSP00000354158.3

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

African (AFR) AF: 0.0827 AC: 317 AN: 3832

American (AMR) AF: 0.300 AC: 737 AN: 2456

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 689 AN: 5074

East Asian (EAS) AF: 0.798 AC: 8968 AN: 11244

South Asian (SAS) AF: 0.432 AC: 299 AN: 692

European-Finnish (FIN) AF: 0.214 AC: 12 AN: 56

Middle Eastern (MID) AF: 0.111 AC: 54 AN: 488

European-Non Finnish (NFE) AF: 0.202 AC: 9988 AN: 49404

Other (OTH) AF: 0.226 AC: 1510 AN: 6690

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

African (AFR) AF: 0.0815 AC: 3384 AN: 41538

American (AMR) AF: 0.261 AC: 3993 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 442 AN: 3466

East Asian (EAS) AF: 0.792 AC: 4093 AN: 5168

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3319 AN: 10564

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14843 AN: 67986

Other (OTH) AF: 0.177 AC: 374 AN: 2116

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
PhyloP100		-0.25
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: rs1064125; hg19: chr12-1600978;