4-71745973-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001204307.1(GC):​c.*25+178C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 151,454 control chromosomes in the GnomAD database, including 80 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 0.027 (80 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0265 (4016/151454) while in subpopulation NFE AF = 0.0392 (2659/67836). AF 95% confidence interval is 0.038. There are 80 homozygotes in GnomAd4. There are 1934 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 80 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4017 AN: 151336 Hom.: 80 Cov.: 27

Gnomad AFR AF: 0.00744

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0197

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

GnomAD4 genome AF: 0.0265 AC: 4016 AN: 151454 Hom.: 80 Cov.: 27 AF XY: 0.0261 AC XY: 1934 AN XY: 74010

African (AFR) AF: 0.00742 AC: 306 AN: 41228

American (AMR) AF: 0.0155 AC: 236 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3468

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5128

South Asian (SAS) AF: 0.0193 AC: 92 AN: 4758

European-Finnish (FIN) AF: 0.0592 AC: 623 AN: 10522

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0392 AC: 2659 AN: 67836

Other (OTH) AF: 0.0195 AC: 41 AN: 2100

Alfa AF: 0.0193 Hom.: 836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.46
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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;