Genetic Variant GC:c.1035-61_1035-42dupAATAAATAAATAAATAAATA (chr4-71755148-C-CTATTTATTTATTTATTTATT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000583.4(GC):c.1035-61_1035-42dupAATAAATAAATAAATAAATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0074 ( 7 hom., cov: 0)

Exomes 𝑓: 0.0021 ( 17 hom. )

Failed GnomAD Quality Control

Consequence

GC
NM_000583.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4 link	c.1035-61_1035-42dupAATAAATAAATAAATAAATA	intron_variant	Intron 8 of 12	ENST00000273951.13	NP_000574.2	P02774-1
GC	NM_001204307.1 link	c.1092-61_1092-42dupAATAAATAAATAAATAAATA	intron_variant	Intron 9 of 13		NP_001191236.1	P02774-3
GC	NM_001204306.1 link	c.1035-61_1035-42dupAATAAATAAATAAATAAATA	intron_variant	Intron 9 of 13		NP_001191235.1	P02774-1
GC	NM_001440458.1 link	c.1035-61_1035-42dupAATAAATAAATAAATAAATA	intron_variant	Intron 8 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13 link	c.1035-61_1035-42dupAATAAATAAATAAATAAATA		intron_variant	Intron 8 of 12	1	NM_000583.4	ENSP00000273951.8		P02774-1

Frequencies

GnomAD3 genomes

AF:

0.00735

AC:

1067

AN:

145144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00562

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.00873

Gnomad SAS

AF:

0.00405

Gnomad FIN

AF:

0.000561

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.00411

Gnomad OTH

AF:

0.00803

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00215

AC:

610

AN:

284194

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

380

AN XY:

157742

show subpopulations

African (AFR)

AF:

0.00452

AC:

AN:

7528

American (AMR)

AF:

0.00176

AC:

AN:

9072

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

103

AN:

6874

East Asian (EAS)

AF:

0.000987

AC:

AN:

10136

South Asian (SAS)

AF:

0.00180

AC:

AN:

16644

European-Finnish (FIN)

AF:

0.000697

AC:

AN:

22950

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

1918

European-Non Finnish (NFE)

AF:

0.00182

AC:

359

AN:

197406

Other (OTH)

AF:

0.00351

AC:

AN:

11666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00736

AC:

1069

AN:

145232

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

512

AN XY:

70312

show subpopulations

African (AFR)

AF:

0.0138

AC:

541

AN:

39224

American (AMR)

AF:

0.00562

AC:

AN:

14420

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3422

East Asian (EAS)

AF:

0.00875

AC:

AN:

4914

South Asian (SAS)

AF:

0.00406

AC:

AN:

4436

European-Finnish (FIN)

AF:

0.000561

AC:

AN:

8910

Middle Eastern (MID)

AF:

0.0208

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00411

AC:

274

AN:

66710

Other (OTH)

AF:

0.00795

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00271

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-71755148-CTATTTATTTATT-CTATTTATTTATTTATTTATTTATTTATTTATT

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