ENST00000504199.5:c.22-4454T>C

Variant names:

• chr4-71788508-A-G
• rs16847036
• ENST00000504199.5:c.22-4454T>C

Variant summary

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

The ENST00000504199.5(GC):​c.22-4454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,800 control chromosomes in the GnomAD database, including 1,473 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 0.12 (1473 hom., cov: 32)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504199.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_001204307.1		c.22-4454T>C		intron	N/A	NP_001191236.1	P02774-3
	GC	NM_001204306.1		c.-36-4454T>C		intron	N/A	NP_001191235.1	P02774-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000504199.5	TSL:1	c.22-4454T>C		intron	N/A	ENSP00000421725.1	P02774-3
	GC	ENST00000882421.1		c.-36-4454T>C		intron	N/A	ENSP00000552480.1
	GC	ENST00000882422.1		c.-188-1584T>C		intron	N/A	ENSP00000552481.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17996 AN: 151682 Hom.: 1466 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.119 AC: 18025 AN: 151800 Hom.: 1473 Cov.: 32 AF XY: 0.115 AC XY: 8550 AN XY: 74182

African (AFR) AF: 0.231 AC: 9554 AN: 41400

American (AMR) AF: 0.101 AC: 1535 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 332 AN: 3460

East Asian (EAS) AF: 0.225 AC: 1151 AN: 5116

South Asian (SAS) AF: 0.0910 AC: 439 AN: 4822

European-Finnish (FIN) AF: 0.0328 AC: 348 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0634 AC: 4303 AN: 67876

Other (OTH) AF: 0.115 AC: 243 AN: 2104

Alfa AF: 0.0886 Hom.: 105

Bravo AF: 0.132

Asia WGS AF: 0.138 AC: 480 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.087
DANN	Benign	0.66
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16847036;

hg19: chr4-72654225;