rs222011

Variant names:

• chr4-71766182-C-A
• rs222011
• NM_000583.4:c.262-539G>T

Variant summary

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

The NM_000583.4(GC):​c.262-539G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,180 control chromosomes in the GnomAD database, including 697 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 0.091 (697 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000583.4. 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_000583.4	MANE Select	c.262-539G>T		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.319-539G>T		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.262-539G>T		intron	N/A	NP_001191235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000273951.13	TSL:1 MANE Select	c.262-539G>T		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.319-539G>T		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.262-539G>T		intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13778 AN: 152062 Hom.: 697 Cov.: 32

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0906 AC: 13795 AN: 152180 Hom.: 697 Cov.: 32 AF XY: 0.0931 AC XY: 6924 AN XY: 74396

African (AFR) AF: 0.0848 AC: 3522 AN: 41536

American (AMR) AF: 0.0504 AC: 771 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4820

European-Finnish (FIN) AF: 0.184 AC: 1947 AN: 10570

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6965 AN: 67994

Other (OTH) AF: 0.0752 AC: 159 AN: 2114

Alfa AF: 0.0958 Hom.: 100

Bravo AF: 0.0825

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.49
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs222011; hg19: chr4-72631899;