4-71742666-T-G

Variant names:

• chr4-71742666-T-G
• rs2282679
• NM_000583.4:c.*26-796A>C

Variant summary

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

The NM_000583.4(GC):​c.*26-796A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,160 control chromosomes in the GnomAD database, including 4,256 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 0.22 (4256 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329
• Publications: 388 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 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.*26-796A>C		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.*26-796A>C		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.*26-796A>C		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.*26-796A>C		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.*26-796A>C		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.1396-796A>C		intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33097 AN: 152042 Hom.: 4252 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.218 AC: 33117 AN: 152160 Hom.: 4256 Cov.: 32 AF XY: 0.213 AC XY: 15860 AN XY: 74382

African (AFR) AF: 0.0877 AC: 3643 AN: 41524

American (AMR) AF: 0.222 AC: 3393 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1325 AN: 5166

South Asian (SAS) AF: 0.286 AC: 1381 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19499 AN: 67986

Other (OTH) AF: 0.230 AC: 484 AN: 2108

Alfa AF: 0.265 Hom.: 26003

Bravo AF: 0.213

Asia WGS AF: 0.228 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.33
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: rs2282679; hg19: chr4-72608383;