rs843007

Positions:

• chr4-71790381-G-A
• chr4-71790381-G-T

Variant summary

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

The ENST00000504199.5(GC):​c.22-6327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,724 control chromosomes in the GnomAD database, including 38,875 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 0.69 (38875 hom., cov: 32)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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 (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_001204306.1	c.-36-6327C>T		intron_variant			NP_001191235.1
GC	NM_001204307.1	c.22-6327C>T		intron_variant			NP_001191236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000504199.5	c.22-6327C>T		intron_variant		1		ENSP00000421725

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105049 AN: 151604 Hom.: 38872 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.693 AC: 105073 AN: 151724 Hom.: 38875 Cov.: 32 AF XY: 0.696 AC XY: 51567 AN XY: 74110

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.719

Alfa AF: 0.705 Hom.: 5489

Bravo AF: 0.674

Asia WGS AF: 0.693 AC: 2404 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs843007; hg19: chr4-72656098;