dbSNP rs145748219: ERGIC1:c.*518C>T (chr5-172915596-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000326654.7(ERGIC1):c.*518C>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 0.00255 in 471,210 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 2 hom. )

Consequence

ERGIC1
ENST00000326654.7 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.226

Publications

0 publications found

Variant links:

Genes affected

ERGIC1 (HGNC:29205): (endoplasmic reticulum-golgi intermediate compartment 1) This gene encodes a cycling membrane protein which is an endoplasmic reticulum-golgi intermediate compartment (ERGIC) protein which interacts with other members of this protein family to increase their turnover. [provided by RefSeq, Jul 2008]

ERGIC1 Gene-Disease associations (from GenCC):

arthrogryposis multiplex congenita 2, neurogenic type
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ERGIC1 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=-0.86).

BP6

Variant 5-172915596-C-T is Benign according to our data. Variant chr5-172915596-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656080.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326654.7. 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
	ERGIC1	NM_001031711.3	MANE Select	c.375+758C>T		intron	N/A	NP_001026881.1	Q969X5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ERGIC1	ENST00000326654.7	TSL:1	c.*518C>T	3_prime_UTR	Exon 5 of 5	ENSP00000325127.3	A0A8J8YV97
ERGIC1	ENST00000393784.8	TSL:1 MANE Select	c.375+758C>T	intron	N/A	ENSP00000377374.3	Q969X5-1
ERGIC1	ENST00000877926.1		c.375+758C>T	intron	N/A	ENSP00000547985.1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00234

AC:

348

AN:

148874

AF XY:

0.00231

show subpopulations

Gnomad AFR exome

AF:

0.000444

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00371

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00132

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.00255

GnomAD4 exome

AF:

0.00256

AC:

817

AN:

318876

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

435

AN XY:

180144

show subpopulations

African (AFR)

AF:

0.000811

AC:

AN:

8634

American (AMR)

AF:

0.00136

AC:

AN:

27288

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

AN:

10786

East Asian (EAS)

AF:

0.00

AC:

AN:

9212

South Asian (SAS)

AF:

0.00154

AC:

AN:

59744

European-Finnish (FIN)

AF:

0.00163

AC:

AN:

27072

Middle Eastern (MID)

AF:

0.00180

AC:

AN:

2784

European-Non Finnish (NFE)

AF:

0.00343

AC:

546

AN:

159030

Other (OTH)

AF:

0.00286

AC:

AN:

14326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

128

171

214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00252

AC:

384

AN:

152334

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

188

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41578

American (AMR)

AF:

0.00131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00420

AC:

286

AN:

68026

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00302

Hom.:

Bravo

AF:

0.00220

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.8

(source)

DANN

Benign

0.94

PhyloP100

0.23

Mutation Taster

=100/0

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