NM_000583.4:c.59-3707G>T

Variant names:

• chr4-71773107-C-A
• rs16847015
• NM_000583.4:c.59-3707G>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.59-3707G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 151,994 control chromosomes in the GnomAD database, including 835 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 0.088 (835 hom., cov: 33)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_000583.4	MANE Select	c.59-3707G>T		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.116-3707G>T		intron	N/A	NP_001191236.1	P02774-3
	GC	NM_001204306.1		c.59-3707G>T		intron	N/A	NP_001191235.1	P02774-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000273951.13	TSL:1 MANE Select	c.59-3707G>T		intron	N/A	ENSP00000273951.8	P02774-1
	GC	ENST00000504199.5	TSL:1	c.116-3707G>T		intron	N/A	ENSP00000421725.1	P02774-3
	GC	ENST00000513476.5	TSL:5	c.59-3707G>T		intron	N/A	ENSP00000426683.1	D6RF35

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13299 AN: 151876 Hom.: 830 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.0876 AC: 13310 AN: 151994 Hom.: 835 Cov.: 33 AF XY: 0.0865 AC XY: 6429 AN XY: 74302

African (AFR) AF: 0.158 AC: 6563 AN: 41480

American (AMR) AF: 0.0867 AC: 1321 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 222 AN: 3464

East Asian (EAS) AF: 0.236 AC: 1215 AN: 5140

South Asian (SAS) AF: 0.0788 AC: 379 AN: 4808

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10610

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0460 AC: 3125 AN: 67936

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0534 Hom.: 116

Bravo AF: 0.0981

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.76
PhyloP100		-0.46
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: rs16847015; hg19: chr4-72638824;