rs222042

chr4-71746899-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.1396-694C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 150,144 control chromosomes in the GnomAD database, including 350 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 0.065 (350 hom., cov: 31)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.1396-694C>T		intron_variant		ENST00000273951.13
GC	NM_001204306.1	c.1396-694C>T		intron_variant
GC	NM_001204307.1	c.1453-694C>T		intron_variant
GC	XM_006714177.3	c.1263-694C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.1396-694C>T		intron_variant		1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9694 AN: 150032 Hom.: 350 Cov.: 31

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0677

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0646 AC: 9698 AN: 150144 Hom.: 350 Cov.: 31 AF XY: 0.0619 AC XY: 4542 AN XY: 73354

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.0190

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0679

Alfa AF: 0.0634 Hom.: 59

Bravo AF: 0.0650

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.1
Dann	Benign	0.49

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: rs222042; hg19: chr4-72612616;