dbSNP rs2070741: GC:c.*26-91A>C (chr4-71741961-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000583.4(GC):c.*26-91A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 698,008 control chromosomes in the GnomAD database, including 2,438 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 0.076 ( 461 hom., cov: 32)

Exomes 𝑓: 0.077 ( 1977 hom. )

Consequence

GC
NM_000583.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.725

Publications

14 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 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	Effect	Exon Rank	Protein
GC	NM_000583.4	MANE Select	c.*26-91A>C	intron	N/A	NP_000574.2
GC	NM_001204307.1		c.*26-91A>C	intron	N/A	NP_001191236.1
GC	NM_001204306.1		c.*26-91A>C	intron	N/A	NP_001191235.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GC	ENST00000273951.13	TSL:1 MANE Select	c.*26-91A>C	intron	N/A	ENSP00000273951.8
GC	ENST00000504199.5	TSL:1	c.*26-91A>C	intron	N/A	ENSP00000421725.1
GC	ENST00000513476.5	TSL:5	c.1396-91A>C	intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11504

AN:

152060

Hom.:

460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0848

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0704

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0733

Gnomad OTH

AF:

0.0776

GnomAD4 exome

AF:

0.0775

AC:

42290

AN:

545830

Hom.:

1977

AF XY:

0.0794

AC XY:

23487

AN XY:

295638

show subpopulations

African (AFR)

AF:

0.0877

AC:

1365

AN:

15568

American (AMR)

AF:

0.0515

AC:

1752

AN:

34016

Ashkenazi Jewish (ASJ)

AF:

0.0678

AC:

1340

AN:

19776

East Asian (EAS)

AF:

0.162

AC:

5196

AN:

31988

South Asian (SAS)

AF:

0.102

AC:

6314

AN:

61966

European-Finnish (FIN)

AF:

0.0218

AC:

726

AN:

33366

Middle Eastern (MID)

AF:

0.125

AC:

503

AN:

4016

European-Non Finnish (NFE)

AF:

0.0722

AC:

22743

AN:

314852

Other (OTH)

AF:

0.0776

AC:

2351

AN:

30282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1946

3892

5837

7783

9729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0756

AC:

11510

AN:

152178

Hom.:

461

Cov.:

AF XY:

0.0739

AC XY:

5500

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0849

AC:

3526

AN:

41520

American (AMR)

AF:

0.0629

AC:

962

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0704

AC:

244

AN:

3466

East Asian (EAS)

AF:

0.167

AC:

861

AN:

5170

South Asian (SAS)

AF:

0.106

AC:

510

AN:

4816

European-Finnish (FIN)

AF:

0.0182

AC:

193

AN:

10608

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0733

AC:

4981

AN:

67990

Other (OTH)

AF:

0.0768

AC:

162

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

542

1084

1626

2168

2710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0770

Hom.:

640

Bravo

AF:

0.0794

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

(source)

DANN

Benign

0.51

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

Computational scores

Splicing

Publications

Other links and lift over