4-71748550-G-C

Position:

• chr4-71748550-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

GC (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_000583.4	c.1396-2345C>G		intron_variant		ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.1453-2345C>G		intron_variant			NP_001191236.1
GC	NM_001204306.1	c.1396-2345C>G		intron_variant			NP_001191235.1
GC	XM_006714177.3	c.1263-2345C>G		intron_variant			XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.1396-2345C>G		intron_variant		1	NM_000583.4	ENSP00000273951.8

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

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.222

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.069
DANN	Benign	0.43

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: rs2298850; hg19: chr4-72614267;