4-71787988-C-T

Variant names:

• chr4-71787988-C-T
• rs6817912
• ENST00000504199.5:c.22-3934G>A

Variant summary

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

The ENST00000504199.5(GC):​c.22-3934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 151,842 control chromosomes in the GnomAD database, including 558 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 0.080 (558 hom., cov: 32)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_001204307.1		c.22-3934G>A		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.-36-3934G>A		intron	N/A	NP_001191235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000504199.5	TSL:1	c.22-3934G>A		intron	N/A	ENSP00000421725.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12216 AN: 151724 Hom.: 556 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0961

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0805 AC: 12223 AN: 151842 Hom.: 558 Cov.: 32 AF XY: 0.0789 AC XY: 5857 AN XY: 74206

African (AFR) AF: 0.0975 AC: 4042 AN: 41476

American (AMR) AF: 0.0867 AC: 1319 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0961 AC: 332 AN: 3456

East Asian (EAS) AF: 0.224 AC: 1148 AN: 5114

South Asian (SAS) AF: 0.0909 AC: 438 AN: 4818

European-Finnish (FIN) AF: 0.0332 AC: 352 AN: 10612

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0632 AC: 4289 AN: 67844

Other (OTH) AF: 0.0880 AC: 185 AN: 2102

Alfa AF: 0.0472 Hom.: 64

Bravo AF: 0.0883

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.68
PhyloP100		-0.36
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: rs6817912; hg19: chr4-72653705;