rs16847054

Positions:

• chr4-71803242-C-T

Variant summary

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

The ENST00000504199.5(GC):​c.21+684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0806 in 152,130 control chromosomes in the GnomAD database, including 564 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 0.081 (564 hom., cov: 33)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_001204306.1	c.-37+2100G>A		intron_variant
GC	NM_001204307.1	c.21+684G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000504199.5	c.21+684G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12261 AN: 152010 Hom.: 562 Cov.: 33

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0330

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0892

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

GnomAD4 genome AF: 0.0806 AC: 12268 AN: 152130 Hom.: 564 Cov.: 33 AF XY: 0.0791 AC XY: 5885 AN XY: 74374

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0917

Gnomad4 FIN AF: 0.0330

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0891

Alfa AF: 0.0668 Hom.: 45

Bravo AF: 0.0886

Asia WGS AF: 0.126 AC: 436 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16847054; hg19: chr4-72668959;