chr4-71752617-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000583.4(GC):c.1296T>G(p.Asp432Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,611,978 control chromosomes in the GnomAD database, including 240,297 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 17944 hom., cov: 32)

Exomes 𝑓: 0.55 ( 222353 hom. )

Consequence

GC
NM_000583.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -3.89

Publications

713 publications found

Variant links:

Genes affected

GC (HGNC:4187): (GC vitamin D binding protein) The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

GC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.460173E-6).

BP6

Variant 4-71752617-A-C is Benign according to our data. Variant chr4-71752617-A-C is described in ClinVar as Benign. ClinVar VariationId is 15987.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GC	NM_000583.4	MANE Select	c.1296T>G	p.Asp432Glu	missense	Exon 11 of 13	NP_000574.2
GC	NM_001204307.1		c.1353T>G	p.Asp451Glu	missense	Exon 12 of 14	NP_001191236.1
GC	NM_001204306.1		c.1296T>G	p.Asp432Glu	missense	Exon 12 of 14	NP_001191235.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GC	ENST00000273951.13	TSL:1 MANE Select	c.1296T>G	p.Asp432Glu	missense	Exon 11 of 13	ENSP00000273951.8
GC	ENST00000504199.5	TSL:1	c.1353T>G	p.Asp451Glu	missense	Exon 12 of 14	ENSP00000421725.1
GC	ENST00000513476.5	TSL:5	c.1296T>G	p.Asp432Glu	missense	Exon 11 of 12	ENSP00000426683.1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68273

AN:

151994

Hom.:

17953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.550

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.469

GnomAD2 exomes

AF:

0.522

AC:

131047

AN:

251206

AF XY:

0.531

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.598

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.675

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.545

AC:

796152

AN:

1459866

Hom.:

222353

Cov.:

AF XY:

0.547

AC XY:

397490

AN XY:

726388

show subpopulations

African (AFR)

AF:

0.149

AC:

4991

AN:

33434

American (AMR)

AF:

0.511

AC:

22813

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

15640

AN:

26122

East Asian (EAS)

AF:

0.269

AC:

10685

AN:

39674

South Asian (SAS)

AF:

0.549

AC:

47299

AN:

86186

European-Finnish (FIN)

AF:

0.669

AC:

35748

AN:

53402

Middle Eastern (MID)

AF:

0.588

AC:

3383

AN:

5756

European-Non Finnish (NFE)

AF:

0.562

AC:

623662

AN:

1110312

Other (OTH)

AF:

0.529

AC:

31931

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17657

35313

52970

70626

88283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17180

34360

51540

68720

85900

<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:

0.449

AC:

68278

AN:

152112

Hom.:

17944

Cov.:

AF XY:

0.459

AC XY:

34100

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.167

AC:

6913

AN:

41516

American (AMR)

AF:

0.518

AC:

7913

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

2067

AN:

3470

East Asian (EAS)

AF:

0.288

AC:

1483

AN:

5150

South Asian (SAS)

AF:

0.550

AC:

2655

AN:

4824

European-Finnish (FIN)

AF:

0.689

AC:

7279

AN:

10572

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.565

AC:

38384

AN:

67992

Other (OTH)

AF:

0.467

AC:

987

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1691

3382

5074

6765

8456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.520

Hom.:

98070

Bravo

AF:

0.420

TwinsUK

AF:

0.559

AC:

2073

ALSPAC

AF:

0.555

AC:

2140

ESP6500AA

AF:

0.174

AC:

765

ESP6500EA

AF:

0.559

AC:

4808

ExAC

AF:

0.516

AC:

62622

Asia WGS

AF:

0.413

AC:

1434

AN:

3478

EpiCase

AF:

0.556

EpiControl

AF:

0.566

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

GC1/GC2 POLYMORPHISM

Benign:1

Jun 01, 1992

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

Periodontitis

Benign:1

Apr 20, 2023

Genetics Laboratory, Lanzhou University

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:case-control

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0010

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.073

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0000045

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PhyloP100

-3.9

PrimateAI

Benign

0.31

PROVEAN

Benign

0.76

REVEL

Benign

0.037

Sift

Benign

0.36

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.040

MutPred

0.39

Gain of glycosylation at T434 (P = 0.0279)

MPC

0.048

ClinPred

0.039

GERP RS

-10

Varity_R

0.17

gMVP

0.21

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over