rs16847024

Variant names:

• chr4-71784962-C-T
• rs16847024
• ENST00000504199.5:c.22-908G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504199.5(GC):​c.22-908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 151,700 control chromosomes in the GnomAD database, including 214 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 0.033 (214 hom., cov: 32)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_001204307.1	c.22-908G>A		intron_variant	Intron 1 of 13		NP_001191236.1
GC	NM_001204306.1	c.-36-908G>A		intron_variant	Intron 1 of 13		NP_001191235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000504199.5	c.22-908G>A		intron_variant	Intron 1 of 13	1		ENSP00000421725.1
GC	ENST00000506245.1	c.-36-908G>A		intron_variant	Intron 1 of 4	3		ENSP00000426718.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4932 AN: 151582 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0361

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000487

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0327 AC: 4956 AN: 151700 Hom.: 214 Cov.: 32 AF XY: 0.0331 AC XY: 2457 AN XY: 74162

African (AFR) AF: 0.0818 AC: 3389 AN: 41448

American (AMR) AF: 0.0310 AC: 471 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.162 AC: 828 AN: 5118

South Asian (SAS) AF: 0.0355 AC: 171 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000487 AC: 33 AN: 67752

Other (OTH) AF: 0.0290 AC: 61 AN: 2104

Alfa AF: 0.0410 Hom.: 101

Bravo AF: 0.0385

Asia WGS AF: 0.119 AC: 414 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.29
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16847024; hg19: chr4-72650679;