chr5-172914966-C-T

Variant names:

Variant summary

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

The ENST00000326654.7(ERGIC1):c.503C>T(p.Ser168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,445,584 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 21 hom., cov: 32)

Exomes 𝑓: 0.012 ( 159 hom. )

Consequence

ERGIC1
ENST00000326654.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.866

Publications

3 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 links:

MIR10523 (HGNC:54013): (microRNA 10523) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR10523 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 (MetaRNN=0.0022776425).

BP6

Variant 5-172914966-C-T is Benign according to our data. Variant chr5-172914966-C-T is described in ClinVar as Benign. ClinVar VariationId is 2656079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 21 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+128C>T		intron	N/A	NP_001026881.1	Q969X5-1
	MIR10523	NR_162113.1		n.-117C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERGIC1	ENST00000326654.7	TSL:1	c.503C>T	p.Ser168Leu	missense	Exon 5 of 5	ENSP00000325127.3	A0A8J8YV97
ERGIC1	ENST00000393784.8	TSL:1 MANE Select	c.375+128C>T		intron	N/A	ENSP00000377374.3	Q969X5-1
ERGIC1	ENST00000877926.1		c.375+128C>T		intron	N/A	ENSP00000547985.1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1634

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.0110

AC:

1794

AN:

163724

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00931

GnomAD4 exome

AF:

0.0116

AC:

15001

AN:

1293320

Hom.:

159

Cov.:

AF XY:

0.0113

AC XY:

7253

AN XY:

643904

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

29540

American (AMR)

AF:

0.00267

AC:

AN:

36288

Ashkenazi Jewish (ASJ)

AF:

0.000978

AC:

AN:

24552

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35728

South Asian (SAS)

AF:

0.00165

AC:

129

AN:

78150

European-Finnish (FIN)

AF:

0.0459

AC:

2281

AN:

49722

Middle Eastern (MID)

AF:

0.00200

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.0121

AC:

11889

AN:

979260

Other (OTH)

AF:

0.00966

AC:

527

AN:

54580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

739

1478

2216

2955

3694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.0107

AC:

1634

AN:

152264

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

930

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

41546

American (AMR)

AF:

0.00333

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0550

AC:

583

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0130

AC:

885

AN:

68012

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

168

252

336

420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00891

Hom.:

Bravo

AF:

0.00683

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00339

AC:

ESP6500EA

AF:

0.0139

AC:

ExAC

AF:

0.00719

AC:

812

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance: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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0070

(source)

DANN

Benign

0.14

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

PhyloP100

-0.87

PROVEAN

Benign

-0.97

REVEL

Benign

0.013

Sift

Pathogenic

0.0

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.057

ClinPred

0.020

GERP RS

-5.0

Mutation Taster

=99/1

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