4-71742398-C-T

Variant names:

• chr4-71742398-C-T
• rs705117
• NM_000583.4:c.*26-528G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000583.4(GC):​c.*26-528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,092 control chromosomes in the GnomAD database, including 39,273 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 0.67 (39273 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.*26-528G>A		intron_variant	Intron 12 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.*26-528G>A		intron_variant	Intron 13 of 13		NP_001191236.1
GC	NM_001204306.1	c.*26-528G>A		intron_variant	Intron 13 of 13		NP_001191235.1
GC	NM_001440458.1	c.*40-528G>A		intron_variant	Intron 11 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.*26-528G>A		intron_variant	Intron 12 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102175 AN: 151974 Hom.: 39273 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.672 AC: 102196 AN: 152092 Hom.: 39273 Cov.: 32 AF XY: 0.676 AC XY: 50296 AN XY: 74372

African (AFR) AF: 0.277 AC: 11495 AN: 41440

American (AMR) AF: 0.738 AC: 11279 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3050 AN: 3466

East Asian (EAS) AF: 0.483 AC: 2485 AN: 5150

South Asian (SAS) AF: 0.832 AC: 4016 AN: 4828

European-Finnish (FIN) AF: 0.887 AC: 9398 AN: 10596

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.852 AC: 57973 AN: 68012

Other (OTH) AF: 0.699 AC: 1475 AN: 2110

Alfa AF: 0.794 Hom.: 152292

Bravo AF: 0.638

Asia WGS AF: 0.620 AC: 2161 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	2.1
DANN	Benign	0.69
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs705117; hg19: chr4-72608115;