4-71745973-G-C

Variant names:

• chr4-71745973-G-C
• rs842999
• NM_000583.4:c.*25+178C>G

Variant summary

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

The NM_001204307.1(GC):​c.*25+178C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,354 control chromosomes in the GnomAD database, including 16,424 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 0.43 (16424 hom., cov: 27)
• Consequence: GC NM_001204307.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204307.1. 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.*25+178C>G		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.*25+178C>G		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.*25+178C>G		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.*25+178C>G		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.*25+178C>G		intron	N/A	ENSP00000421725.1
	GC	ENST00000882431.1		c.*81C>G		3_prime_UTR	Exon 13 of 13	ENSP00000552490.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64892 AN: 151236 Hom.: 16434 Cov.: 27

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.429 AC: 64888 AN: 151354 Hom.: 16424 Cov.: 27 AF XY: 0.439 AC XY: 32437 AN XY: 73932

African (AFR) AF: 0.153 AC: 6288 AN: 41194

American (AMR) AF: 0.501 AC: 7607 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3466

East Asian (EAS) AF: 0.226 AC: 1159 AN: 5124

South Asian (SAS) AF: 0.531 AC: 2522 AN: 4748

European-Finnish (FIN) AF: 0.669 AC: 7038 AN: 10516

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36720 AN: 67812

Other (OTH) AF: 0.450 AC: 945 AN: 2098

Alfa AF: 0.323 Hom.: 836

Bravo AF: 0.411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.45
PhyloP100		-0.30
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: rs842999; hg19: chr4-72611690;