chr4-71746970-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000583.4(GC):​c.1396-765G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 151,764 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 424 hom., cov: 31)

Consequence

GC
NM_000583.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319

Publications

9 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GCNM_000583.4 linkc.1396-765G>C intron_variant Intron 11 of 12 ENST00000273951.13 NP_000574.2 P02774-1
GCNM_001204307.1 linkc.1453-765G>C intron_variant Intron 12 of 13 NP_001191236.1 P02774-3
GCNM_001204306.1 linkc.1396-765G>C intron_variant Intron 12 of 13 NP_001191235.1 P02774-1
GCNM_001440458.1 linkc.1263-765G>C intron_variant Intron 10 of 11 NP_001427387.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GCENST00000273951.13 linkc.1396-765G>C intron_variant Intron 11 of 12 1 NM_000583.4 ENSP00000273951.8 P02774-1

Frequencies

GnomAD3 genomes
AF:
0.0722
AC:
10952
AN:
151646
Hom.:
423
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0730
Gnomad AMI
AF:
0.0474
Gnomad AMR
AF:
0.0615
Gnomad ASJ
AF:
0.0686
Gnomad EAS
AF:
0.166
Gnomad SAS
AF:
0.111
Gnomad FIN
AF:
0.0184
Gnomad MID
AF:
0.0981
Gnomad NFE
AF:
0.0730
Gnomad OTH
AF:
0.0723
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0722
AC:
10955
AN:
151764
Hom.:
424
Cov.:
31
AF XY:
0.0708
AC XY:
5250
AN XY:
74176
show subpopulations
African (AFR)
AF:
0.0731
AC:
3023
AN:
41342
American (AMR)
AF:
0.0615
AC:
936
AN:
15216
Ashkenazi Jewish (ASJ)
AF:
0.0686
AC:
238
AN:
3468
East Asian (EAS)
AF:
0.166
AC:
855
AN:
5146
South Asian (SAS)
AF:
0.109
AC:
525
AN:
4804
European-Finnish (FIN)
AF:
0.0184
AC:
194
AN:
10544
Middle Eastern (MID)
AF:
0.0952
AC:
28
AN:
294
European-Non Finnish (NFE)
AF:
0.0730
AC:
4963
AN:
67944
Other (OTH)
AF:
0.0715
AC:
150
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
514
1029
1543
2058
2572
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
128
256
384
512
640
<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:
0.0252
Hom.:
14
Bravo
AF:
0.0751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
2.3
DANN
Benign
0.76
PhyloP100
-0.32
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12640179; hg19: chr4-72612687; API