dbSNP rs222016: GC:c.128+73C>T (chr4-71769258-G-A) – 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.128+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,138,650 control chromosomes in the GnomAD database, including 380,913 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 0.73 ( 42415 hom., cov: 31)

Exomes 𝑓: 0.82 ( 338498 hom. )

Consequence

GC
NM_000583.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

21 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.844 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.128+73C>T	intron	N/A	NP_000574.2
GC	NM_001204307.1		c.185+73C>T	intron	N/A	NP_001191236.1
GC	NM_001204306.1		c.128+73C>T	intron	N/A	NP_001191235.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GC	ENST00000273951.13	TSL:1 MANE Select	c.128+73C>T	intron	N/A	ENSP00000273951.8
GC	ENST00000504199.5	TSL:1	c.185+73C>T	intron	N/A	ENSP00000421725.1
GC	ENST00000513476.5	TSL:5	c.128+73C>T	intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110428

AN:

151892

Hom.:

42411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.854

Gnomad FIN

AF:

0.796

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.850

Gnomad OTH

AF:

0.758

GnomAD4 exome

AF:

0.825

AC:

813767

AN:

986640

Hom.:

338498

AF XY:

0.828

AC XY:

420290

AN XY:

507504

show subpopulations

African (AFR)

AF:

0.456

AC:

11138

AN:

24404

American (AMR)

AF:

0.775

AC:

31399

AN:

40510

Ashkenazi Jewish (ASJ)

AF:

0.900

AC:

20019

AN:

22232

East Asian (EAS)

AF:

0.643

AC:

23824

AN:

37060

South Asian (SAS)

AF:

0.852

AC:

62107

AN:

72938

European-Finnish (FIN)

AF:

0.803

AC:

41115

AN:

51174

Middle Eastern (MID)

AF:

0.823

AC:

3998

AN:

4856

European-Non Finnish (NFE)

AF:

0.848

AC:

584388

AN:

688974

Other (OTH)

AF:

0.804

AC:

35779

AN:

44492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6590

13180

19769

26359

32949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10464

20928

31392

41856

52320

<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:

0.727

AC:

110463

AN:

152010

Hom.:

42415

Cov.:

AF XY:

0.727

AC XY:

54053

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.459

AC:

19000

AN:

41420

American (AMR)

AF:

0.807

AC:

12327

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3139

AN:

3472

East Asian (EAS)

AF:

0.601

AC:

3094

AN:

5148

South Asian (SAS)

AF:

0.854

AC:

4113

AN:

4814

European-Finnish (FIN)

AF:

0.796

AC:

8430

AN:

10594

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.850

AC:

57782

AN:

67980

Other (OTH)

AF:

0.759

AC:

1602

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1323

2645

3968

5290

6613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.805

Hom.:

151720

Bravo

AF:

0.709

Asia WGS

AF:

0.702

AC:

2442

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.012

(source)

DANN

Benign

0.48

PhyloP100

-1.9

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