Genetic Variant GC:c.1035-45_1035-42delAATA (chr4-71755148-CTATT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

-4

BS2

The NM_000583.4(GC):c.1035-45_1035-42delAATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000605 in 429,452 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

GC
NM_000583.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.720

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 GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4 link	c.1035-45_1035-42delAATA	intron_variant	Intron 8 of 12	ENST00000273951.13	NP_000574.2	P02774-1
GC	NM_001204307.1 link	c.1092-45_1092-42delAATA	intron_variant	Intron 9 of 13		NP_001191236.1	P02774-3
GC	NM_001204306.1 link	c.1035-45_1035-42delAATA	intron_variant	Intron 9 of 13		NP_001191235.1	P02774-1
GC	NM_001440458.1 link	c.1035-45_1035-42delAATA	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.1035-45_1035-42delAATA		intron_variant	Intron 8 of 12	1	NM_000583.4	ENSP00000273951.8		P02774-1

Frequencies

GnomAD3 genomes

AF:

0.000902

AC:

131

AN:

145156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000486

Gnomad ASJ

AF:

0.000584

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.000674

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000195

Gnomad OTH

AF:

0.00100

GnomAD4 exome

AF:

0.000447

AC:

127

AN:

284208

Hom.:

AF XY:

0.000469

AC XY:

AN XY:

157752

show subpopulations

African (AFR)

AF:

0.00346

AC:

AN:

7522

American (AMR)

AF:

0.000331

AC:

AN:

9070

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

6876

East Asian (EAS)

AF:

0.0000987

AC:

AN:

10136

South Asian (SAS)

AF:

0.000661

AC:

AN:

16644

European-Finnish (FIN)

AF:

0.000218

AC:

AN:

22950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1918

European-Non Finnish (NFE)

AF:

0.000329

AC:

AN:

197428

Other (OTH)

AF:

0.000686

AC:

AN:

11664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000916

AC:

133

AN:

145244

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

AN XY:

70318

show subpopulations

African (AFR)

AF:

0.00265

AC:

104

AN:

39232

American (AMR)

AF:

0.000485

AC:

AN:

14420

Ashkenazi Jewish (ASJ)

AF:

0.000584

AC:

AN:

3422

East Asian (EAS)

AF:

0.000204

AC:

AN:

4914

South Asian (SAS)

AF:

0.000676

AC:

AN:

4436

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

8910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000195

AC:

AN:

66714

Other (OTH)

AF:

0.000994

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000208

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.72

Mutation Taster

=100/0

polymorphism

(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