4-71752640-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000583.4(GC):c.1273C>A(p.Arg425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000531 in 1,612,574 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: GC NM_000583.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.206

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-71752640-G-T is Benign according to our data. Variant chr4-71752640-G-T is described in ClinVar as [Benign]. Clinvar id is 787805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.206 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.1273C>A	p.Arg425=	synonymous_variant	11/13	ENST00000273951.13
GC	NM_001204307.1	c.1330C>A	p.Arg444=	synonymous_variant	12/14
GC	NM_001204306.1	c.1273C>A	p.Arg425=	synonymous_variant	12/14
GC	XM_006714177.3	c.1262+1771C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.1273C>A	p.Arg425=	synonymous_variant	11/13	1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152102 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00659

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000582 AC: 146 AN: 250922 Hom.: 0 AF XY: 0.000406 AC XY: 55 AN XY: 135626

Gnomad AFR exome AF: 0.00671

Gnomad AMR exome AF: 0.000611

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000373 AC: 545 AN: 1460354 Hom.: 1 Cov.: 31 AF XY: 0.000321 AC XY: 233 AN XY: 726542

Gnomad4 AFR exome AF: 0.00691

Gnomad4 AMR exome AF: 0.000740

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000213

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.00205 AC: 312 AN: 152220 Hom.: 1 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74430

Gnomad4 AFR AF: 0.00657

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000679 Hom.: 0

Bravo AF: 0.00231

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.86
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs137942674; hg19: chr4-72618357;