dbSNP rs138791726: ERC1:p.Tyr100Tyr (chr12-1028203-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_178040.4(ERC1):c.300C>T(p.Tyr100Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,614,166 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

ERC1
NM_178040.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.69

Publications

1 publications found

Variant links:

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]

ERC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 12-1028203-C-T is Benign according to our data. Variant chr12-1028203-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3038730.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.69 with no splicing effect.

BS2

High AC in GnomAd4 at 168 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERC1	NM_178040.4	MANE Select	c.300C>T	p.Tyr100Tyr	synonymous	Exon 2 of 19	NP_829884.1	Q8IUD2-1
ERC1	NM_178039.4		c.300C>T	p.Tyr100Tyr	synonymous	Exon 2 of 18	NP_829883.1	Q8IUD2-3
ERC1	NM_001301248.1		c.300C>T	p.Tyr100Tyr	synonymous	Exon 1 of 19	NP_001288177.1	G8JLD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERC1	ENST00000360905.9	TSL:1 MANE Select	c.300C>T	p.Tyr100Tyr	synonymous	Exon 2 of 19	ENSP00000354158.3	Q8IUD2-1
ERC1	ENST00000589028.6	TSL:1	c.300C>T	p.Tyr100Tyr	synonymous	Exon 3 of 20	ENSP00000468263.1	Q8IUD2-1
ERC1	ENST00000543086.7	TSL:1	c.300C>T	p.Tyr100Tyr	synonymous	Exon 2 of 18	ENSP00000438546.1	Q8IUD2-3

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000966

AC:

243

AN:

251462

AF XY:

0.000898

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00224

AC:

3276

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1591

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00278

AC:

3087

AN:

1112012

Other (OTH)

AF:

0.00189

AC:

114

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

203

406

610

813

1016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152274

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000553

AC:

AN:

41556

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00188

AC:

128

AN:

68024

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00113

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ERC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.11

(source)

DANN

Benign

0.68

PhyloP100

-1.7

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over