Genetic Variant NM_000583.4:c.-39C>T (chr4-71784057-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000583.4(GC):c.-39C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,586,812 control chromosomes in the GnomAD database, including 9,246 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 0.13 ( 1866 hom., cov: 32)

Exomes 𝑓: 0.079 ( 7380 hom. )

Consequence

GC
NM_000583.4 5_prime_UTR

Scores

Splicing: ADA: 0.0003753

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4 link	c.-39C>T	5_prime_UTR_variant	Exon 1 of 13	ENST00000273951.13	NP_000574.2	P02774-1
GC	XM_006714177.3 link	c.-39C>T	5_prime_UTR_variant	Exon 1 of 12		XP_006714240.1
GC	NM_001204307.1 link	c.22-3C>T	splice_region_variant, intron_variant	Intron 1 of 13		NP_001191236.1	P02774-3
GC	NM_001204306.1 link	c.-36-3C>T	splice_region_variant, intron_variant	Intron 1 of 13		NP_001191235.1	P02774-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13 link	c.-39C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_000583.4	ENSP00000273951.8		P02774-1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19384

AN:

151372

Hom.:

1859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0955

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0597

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.122

AC:

28747

AN:

236118

Hom.:

2902

AF XY:

0.114

AC XY:

14621

AN XY:

127720

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.0936

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0361

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.0791

AC:

113497

AN:

1435320

Hom.:

7380

Cov.:

AF XY:

0.0796

AC XY:

56804

AN XY:

713592

show subpopulations

Gnomad4 AFR exome

AF:

0.247

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0908

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.0348

Gnomad4 NFE exome

AF:

0.0578

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.128

AC:

19420

AN:

151492

Hom.:

1866

Cov.:

AF XY:

0.126

AC XY:

9352

AN XY:

74016

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.0955

Gnomad4 EAS

AF:

0.386

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0323

Gnomad4 NFE

AF:

0.0597

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.0774

Hom.:

1416

Bravo

AF:

0.144

Asia WGS

AF:

0.251

AC:

872

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.5

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00038

dbscSNV1_RF

Benign

0.0020

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over