NM_000583.4:c.*26-91A>C

Variant names:

• chr4-71741961-T-G
• rs2070741
• NM_000583.4:c.*26-91A>C

Variant summary

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

The NM_000583.4(GC):​c.*26-91A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 698,008 control chromosomes in the GnomAD database, including 2,438 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 0.076 (461 hom., cov: 32)
  • Exomes 𝑓: 0.077 (1977 hom.)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 14 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.*26-91A>C		intron_variant	Intron 12 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.*26-91A>C		intron_variant	Intron 13 of 13		NP_001191236.1
GC	NM_001204306.1	c.*26-91A>C		intron_variant	Intron 13 of 13		NP_001191235.1
GC	NM_001440458.1	c.*40-91A>C		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.*26-91A>C		intron_variant	Intron 12 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11504 AN: 152060 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0776

GnomAD4 exome AF: 0.0775 AC: 42290 AN: 545830 Hom.: 1977 AF XY: 0.0794 AC XY: 23487 AN XY: 295638

African (AFR) AF: 0.0877 AC: 1365 AN: 15568

American (AMR) AF: 0.0515 AC: 1752 AN: 34016

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 1340 AN: 19776

East Asian (EAS) AF: 0.162 AC: 5196 AN: 31988

South Asian (SAS) AF: 0.102 AC: 6314 AN: 61966

European-Finnish (FIN) AF: 0.0218 AC: 726 AN: 33366

Middle Eastern (MID) AF: 0.125 AC: 503 AN: 4016

European-Non Finnish (NFE) AF: 0.0722 AC: 22743 AN: 314852

Other (OTH) AF: 0.0776 AC: 2351 AN: 30282

GnomAD4 genome AF: 0.0756 AC: 11510 AN: 152178 Hom.: 461 Cov.: 32 AF XY: 0.0739 AC XY: 5500 AN XY: 74416

African (AFR) AF: 0.0849 AC: 3526 AN: 41520

American (AMR) AF: 0.0629 AC: 962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3466

East Asian (EAS) AF: 0.167 AC: 861 AN: 5170

South Asian (SAS) AF: 0.106 AC: 510 AN: 4816

European-Finnish (FIN) AF: 0.0182 AC: 193 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4981 AN: 67990

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0770 Hom.: 640

Bravo AF: 0.0794

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.72
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: rs2070741; hg19: chr4-72607678; COSMIC: COSV56738418;