rs2298849

Positions:

• chr4-71783134-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000583.4(GC):​c.58+827T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,644 control chromosomes in the GnomAD database, including 5,420 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 0.25 (5420 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.58+827T>C		intron_variant		ENST00000273951.13
GC	NM_001204306.1	c.58+827T>C		intron_variant
GC	NM_001204307.1	c.115+827T>C		intron_variant
GC	XM_006714177.3	c.58+827T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.58+827T>C		intron_variant		1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38262 AN: 151526 Hom.: 5408 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.253 AC: 38320 AN: 151644 Hom.: 5420 Cov.: 32 AF XY: 0.252 AC XY: 18676 AN XY: 74130

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.247

Alfa AF: 0.204 Hom.: 1581

Bravo AF: 0.263

Asia WGS AF: 0.287 AC: 994 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2298849; hg19: chr4-72648851;