4-71788550-C-T

Variant names:

• chr4-71788550-C-T
• rs16847039
• ENST00000504199.5:c.22-4496G>A

Variant summary

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

The ENST00000504199.5(GC):​c.22-4496G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 147,688 control chromosomes in the GnomAD database, including 4,822 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 0.24 (4822 hom., cov: 30)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_001204307.1	c.22-4496G>A		intron_variant	Intron 1 of 13		NP_001191236.1
GC	NM_001204306.1	c.-36-4496G>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.22-4496G>A		intron_variant	Intron 1 of 13	1		ENSP00000421725.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 35673 AN: 147566 Hom.: 4803 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.242 AC: 35737 AN: 147688 Hom.: 4822 Cov.: 30 AF XY: 0.241 AC XY: 17248 AN XY: 71706

African (AFR) AF: 0.386 AC: 15514 AN: 40240

American (AMR) AF: 0.179 AC: 2599 AN: 14496

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 557 AN: 3434

East Asian (EAS) AF: 0.232 AC: 1162 AN: 5000

South Asian (SAS) AF: 0.138 AC: 649 AN: 4702

European-Finnish (FIN) AF: 0.220 AC: 2139 AN: 9744

Middle Eastern (MID) AF: 0.268 AC: 76 AN: 284

European-Non Finnish (NFE) AF: 0.185 AC: 12360 AN: 66838

Other (OTH) AF: 0.234 AC: 480 AN: 2048

Alfa AF: 0.198 Hom.: 418

Bravo AF: 0.244

Asia WGS AF: 0.176 AC: 610 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.84
DANN	Benign	0.45
PhyloP100		-0.68
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: rs16847039; hg19: chr4-72654267;