Menu
GeneBe

rs7041

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.45 ( 17944 hom., cov: 32)
Exomes 𝑓: 0.55 ( 222353 hom. )

Consequence

GC
NM_000583.4 missense

Scores

18

Clinical Significance

Benign no assertion criteria provided B:2

Conservation

PhyloP100: -3.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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 id is 15987.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCNM_000583.4 linkuse as main transcriptc.1296T>G p.Asp432Glu missense_variant 11/13 ENST00000273951.13
GCNM_001204307.1 linkuse as main transcriptc.1353T>G p.Asp451Glu missense_variant 12/14
GCNM_001204306.1 linkuse as main transcriptc.1296T>G p.Asp432Glu missense_variant 12/14
GCXM_006714177.3 linkuse as main transcriptc.1262+1794T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCENST00000273951.13 linkuse as main transcriptc.1296T>G p.Asp432Glu missense_variant 11/131 NM_000583.4 P1P02774-1

Frequencies

GnomAD3 genomes
AF:
0.449
AC:
68273
AN:
151994
Hom.:
17953
Cov.:
32
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
GnomAD3 exomes
AF:
0.522
AC:
131047
AN:
251206
Hom.:
36331
AF XY:
0.531
AC XY:
72119
AN XY:
135784
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 SAS exome
AF:
0.551
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.:
34
AF XY:
0.547
AC XY:
397490
AN XY:
726388
show subpopulations
Gnomad4 AFR exome
AF:
0.149
Gnomad4 AMR exome
AF:
0.511
Gnomad4 ASJ exome
AF:
0.599
Gnomad4 EAS exome
AF:
0.269
Gnomad4 SAS exome
AF:
0.549
Gnomad4 FIN exome
AF:
0.669
Gnomad4 NFE exome
AF:
0.562
Gnomad4 OTH exome
AF:
0.529
GnomAD4 genome
AF:
0.449
AC:
68278
AN:
152112
Hom.:
17944
Cov.:
32
AF XY:
0.459
AC XY:
34100
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.167
Gnomad4 AMR
AF:
0.518
Gnomad4 ASJ
AF:
0.596
Gnomad4 EAS
AF:
0.288
Gnomad4 SAS
AF:
0.550
Gnomad4 FIN
AF:
0.689
Gnomad4 NFE
AF:
0.565
Gnomad4 OTH
AF:
0.467
Alfa
AF:
0.538
Hom.:
52790
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:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

GC1/GC2 POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMJun 01, 1992- -
Periodontitis Benign:1
Benign, no assertion criteria providedcase-controlGenetics Laboratory, Lanzhou UniversityApr 20, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.87
T
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.0010
Dann
Benign
0.46
DEOGEN2
Benign
0.073
T;.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.010
N
LIST_S2
Benign
0.42
T;T;T
MetaRNN
Benign
0.0000045
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.6
L;.;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.76
N;N;N
REVEL
Benign
0.037
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.20
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.040
MutPred
0.39
Gain of glycosylation at T434 (P = 0.0279);.;Gain of glycosylation at T434 (P = 0.0279);
MPC
0.048
ClinPred
0.039
T
GERP RS
-10
Varity_R
0.17
gMVP
0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7041; hg19: chr4-72618334; COSMIC: COSV56735134; API