12-1486417-CTTTAT-CTTTATTTTATTTTAT

Variant names:

• chr12-1486417-C-CTTTATTTTAT
• rs75172865
• NM_178040.4:c.3214-3662_3214-3653dupATTTTATTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178040.4(ERC1):​c.3214-3662_3214-3653dupATTTTATTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 150,964 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: ERC1 NM_178040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178040.4. 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
	ERC1	NM_178040.4	MANE Select	c.3214-3662_3214-3653dupATTTTATTTT		intron	N/A	NP_829884.1	Q8IUD2-1
	ERC1	NM_178039.4		c.3130-3662_3130-3653dupATTTTATTTT		intron	N/A	NP_829883.1	Q8IUD2-3
	ERC1	NM_001301248.1		c.*9-3662_*9-3653dupATTTTATTTT		intron	N/A	NP_001288177.1	G8JLD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERC1	ENST00000360905.9	TSL:1 MANE Select	c.3214-3676_3214-3675insTTTATTTTAT		intron	N/A	ENSP00000354158.3	Q8IUD2-1
	ERC1	ENST00000589028.6	TSL:1	c.3214-3676_3214-3675insTTTATTTTAT		intron	N/A	ENSP00000468263.1	Q8IUD2-1
	ERC1	ENST00000543086.7	TSL:1	c.3130-3676_3130-3675insTTTATTTTAT		intron	N/A	ENSP00000438546.1	Q8IUD2-3

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 150964 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 150964 Hom.: 0 Cov.: 34 AF XY: 0.0000136 AC XY: 1 AN XY: 73658

African (AFR) AF: 0.00 AC: 0 AN: 41070

American (AMR) AF: 0.00 AC: 0 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67730

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75172865; hg19: chr12-1595583;