rs705120

Positions:

• chr4-71748423-A-C
• chr4-71748423-A-T

Variant summary

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

The NM_000583.4(GC):​c.1396-2218T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,570 control chromosomes in the GnomAD database, including 26,733 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 0.59 (26733 hom., cov: 30)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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 (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_000583.4	c.1396-2218T>G		intron_variant		ENST00000273951.13	NP_000574.2
GC	NM_001204306.1	c.1396-2218T>G		intron_variant			NP_001191235.1
GC	NM_001204307.1	c.1453-2218T>G		intron_variant			NP_001191236.1
GC	XM_006714177.3	c.1263-2218T>G		intron_variant			XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.1396-2218T>G		intron_variant		1	NM_000583.4	ENSP00000273951	P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89506 AN: 151452 Hom.: 26723 Cov.: 30

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.591 AC: 89559 AN: 151570 Hom.: 26733 Cov.: 30 AF XY: 0.602 AC XY: 44609 AN XY: 74046

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.587

Alfa AF: 0.588 Hom.: 44595

Bravo AF: 0.579

Asia WGS AF: 0.620 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.32

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: rs705120; hg19: chr4-72614140;