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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4 link	c.*26-91A>C	intron_variant	Intron 12 of 12	ENST00000273951.13	NP_000574.2	P02774-1
GC	NM_001204307.1 link	c.*26-91A>C	intron_variant	Intron 13 of 13		NP_001191236.1	P02774-3
GC	NM_001204306.1 link	c.*26-91A>C	intron_variant	Intron 13 of 13		NP_001191235.1	P02774-1
GC	NM_001440458.1 link	c.*40-91A>C	intron_variant	Intron 11 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13 link	c.*26-91A>C		intron_variant	Intron 12 of 12	1	NM_000583.4	ENSP00000273951.8		P02774-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over