rs1352843

Positions:

• chr4-71777237-T-C
• chr4-71777237-T-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+6724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 151,862 control chromosomes in the GnomAD database, including 693 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 0.089 (693 hom., cov: 31)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.423

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_000583.4	c.58+6724A>G		intron_variant		ENST00000273951.13	NP_000574.2
GC	NM_001204306.1	c.58+6724A>G		intron_variant			NP_001191235.1
GC	NM_001204307.1	c.115+6724A>G		intron_variant			NP_001191236.1
GC	XM_006714177.3	c.58+6724A>G		intron_variant			XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.58+6724A>G		intron_variant		1	NM_000583.4	ENSP00000273951	P1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13514 AN: 151744 Hom.: 693 Cov.: 31

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0745

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

GnomAD4 genome AF: 0.0891 AC: 13527 AN: 151862 Hom.: 693 Cov.: 31 AF XY: 0.0914 AC XY: 6787 AN XY: 74230

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0309

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0508 Hom.: 63

Bravo AF: 0.0808

Asia WGS AF: 0.0190 AC: 66 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.58

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: rs1352843; hg19: chr4-72642954;