4-71748550-G-C

Variant names:

• chr4-71748550-G-C
• rs2298850
• NM_000583.4:c.1396-2345C>G

Variant summary

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

The NM_000583.4(GC):​c.1396-2345C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,020 control chromosomes in the GnomAD database, including 3,748 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 0.20 (3748 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 48 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 (SAS) allele frequency at 95% confidence interval = 0.268 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.1396-2345C>G		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.1453-2345C>G		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.1396-2345C>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.1396-2345C>G		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.1453-2345C>G		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.1395+3968C>G		intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30880 AN: 151902 Hom.: 3745 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.203 AC: 30898 AN: 152020 Hom.: 3748 Cov.: 32 AF XY: 0.198 AC XY: 14719 AN XY: 74276

African (AFR) AF: 0.0722 AC: 2996 AN: 41512

American (AMR) AF: 0.213 AC: 3252 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 983 AN: 3466

East Asian (EAS) AF: 0.258 AC: 1330 AN: 5158

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4812

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10574

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18428 AN: 67910

Other (OTH) AF: 0.222 AC: 469 AN: 2110

Alfa AF: 0.138 Hom.: 261

Bravo AF: 0.201

Asia WGS AF: 0.227 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.069
DANN	Benign	0.43
PhyloP100		-2.0
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: rs2298850; hg19: chr4-72614267;