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GeneBe

4-71765497-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000583.4(GC):c.408C>T(p.Tyr136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,613,940 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 53 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 45 hom. )

Consequence

GC
NM_000583.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-71765497-G-A is Benign according to our data. Variant chr4-71765497-G-A is described in ClinVar as [Benign]. Clinvar id is 784040.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.98 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCNM_000583.4 linkuse as main transcriptc.408C>T p.Tyr136= synonymous_variant 4/13 ENST00000273951.13
GCNM_001204307.1 linkuse as main transcriptc.465C>T p.Tyr155= synonymous_variant 5/14
GCNM_001204306.1 linkuse as main transcriptc.408C>T p.Tyr136= synonymous_variant 5/14
GCXM_006714177.3 linkuse as main transcriptc.408C>T p.Tyr136= synonymous_variant 4/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCENST00000273951.13 linkuse as main transcriptc.408C>T p.Tyr136= synonymous_variant 4/131 NM_000583.4 P1P02774-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0147
AC:
2236
AN:
152096
Hom.:
53
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0505
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00603
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00103
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.0172
GnomAD3 exomes
AF:
0.00372
AC:
934
AN:
251030
Hom.:
14
AF XY:
0.00293
AC XY:
397
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.0503
Gnomad AMR exome
AF:
0.00197
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.000784
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00159
AC:
2321
AN:
1461726
Hom.:
45
Cov.:
31
AF XY:
0.00139
AC XY:
1008
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0538
Gnomad4 AMR exome
AF:
0.00250
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000765
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.00421
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0147
AC:
2241
AN:
152214
Hom.:
53
Cov.:
32
AF XY:
0.0143
AC XY:
1065
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0505
Gnomad4 AMR
AF:
0.00595
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.0180
Alfa
AF:
0.00599
Hom.:
12
Bravo
AF:
0.0169
Asia WGS
AF:
0.0130
AC:
44
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.069
Dann
Benign
0.69

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

LitVar

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

Other links and lift over

dbSNP: rs58801122; hg19: chr4-72631214; API