rs222016

Positions:

• chr4-71769258-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000583.4(GC):​c.128+73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,138,650 control chromosomes in the GnomAD database, including 380,913 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 0.73 (42415 hom., cov: 31)
  • Exomes 𝑓: 0.82 (338498 hom.)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.128+73C>T		intron_variant		ENST00000273951.13
GC	NM_001204306.1	c.128+73C>T		intron_variant
GC	NM_001204307.1	c.185+73C>T		intron_variant
GC	XM_006714177.3	c.128+73C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.128+73C>T		intron_variant		1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110428 AN: 151892 Hom.: 42411 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.825 AC: 813767 AN: 986640 Hom.: 338498 AF XY: 0.828 AC XY: 420290 AN XY: 507504

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.900

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.852

Gnomad4 FIN exome AF: 0.803

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.727 AC: 110463 AN: 152010 Hom.: 42415 Cov.: 31 AF XY: 0.727 AC XY: 54053 AN XY: 74300

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.759

Alfa AF: 0.829 Hom.: 69841

Bravo AF: 0.709

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs222016; hg19: chr4-72634975; COSMIC: COSV56737041;