rs16847015

chr4-71773107-C-Achr4-71773107-C-T

Variant summary

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

The NM_000583.4(GC):c.59-3707G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 151,994 control chromosomes in the GnomAD database, including 835 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 0.088 (835 hom., cov: 33)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.59-3707G>T		intron_variant		ENST00000273951.13
GC	NM_001204306.1	c.59-3707G>T		intron_variant
GC	NM_001204307.1	c.116-3707G>T		intron_variant
GC	XM_006714177.3	c.59-3707G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.59-3707G>T		intron_variant		1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13299 AN: 151876 Hom.: 830 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.0876 AC: 13310 AN: 151994 Hom.: 835 Cov.: 33 AF XY: 0.0865 AC XY: 6429 AN XY: 74302

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.0641

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.0187

Gnomad4 NFE AF: 0.0460

Gnomad4 OTH AF: 0.0952

Alfa AF: 0.0534 Hom.: 116

Bravo AF: 0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.8
Dann	Benign	0.76

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: rs16847015; hg19: chr4-72638824;