4-71763422-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_000583.4(GC):c.687G>A(p.Lys229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,584,002 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: GC NM_000583.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0530

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 4-71763422-C-T is Benign according to our data. Variant chr4-71763422-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.053 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.687G>A	p.Lys229=	synonymous_variant	6/13	ENST00000273951.13
GC	NM_001204307.1	c.744G>A	p.Lys248=	synonymous_variant	7/14
GC	NM_001204306.1	c.687G>A	p.Lys229=	synonymous_variant	7/14
GC	XM_006714177.3	c.687G>A	p.Lys229=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.687G>A	p.Lys229=	synonymous_variant	6/13	1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 197 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00145 AC: 362 AN: 250292 Hom.: 1 AF XY: 0.00121 AC XY: 163 AN XY: 135252

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.00706

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000657

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00127 AC: 1823 AN: 1431710 Hom.: 3 Cov.: 26 AF XY: 0.00125 AC XY: 891 AN XY: 714134

Gnomad4 AFR exome AF: 0.000335

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.00715

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000819

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00132

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00129 AC: 197 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.00122 AC XY: 91 AN XY: 74456

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00148

Asia WGS AF: 0.000289 AC: 1 AN: 3474

EpiCase AF: 0.00181

EpiControl AF: 0.00208

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	GC: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Aug 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	5.7
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs111261486; hg19: chr4-72629139;