rs222035

Variant names:

• chr4-71755957-T-G
• rs222035
• NM_000583.4:c.1034+755A>C

Variant summary

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

The NM_001204307.1(GC):​c.1091+755A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,160 control chromosomes in the GnomAD database, including 17,493 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 0.44 (17493 hom., cov: 35)
• Consequence: GC NM_001204307.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 13 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 (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_000583.4	MANE Select	c.1034+755A>C		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.1091+755A>C		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.1034+755A>C		intron	N/A	NP_001191235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000273951.13	TSL:1 MANE Select	c.1034+755A>C		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.1091+755A>C		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.1034+755A>C		intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66731 AN: 152042 Hom.: 17502 Cov.: 35

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.439 AC: 66725 AN: 152160 Hom.: 17493 Cov.: 35 AF XY: 0.448 AC XY: 33323 AN XY: 74372

African (AFR) AF: 0.141 AC: 5875 AN: 41556

American (AMR) AF: 0.512 AC: 7827 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2076 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1457 AN: 5178

South Asian (SAS) AF: 0.548 AC: 2648 AN: 4828

European-Finnish (FIN) AF: 0.683 AC: 7221 AN: 10566

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38056 AN: 67962

Other (OTH) AF: 0.459 AC: 969 AN: 2112

Alfa AF: 0.482 Hom.: 2657

Bravo AF: 0.410

Asia WGS AF: 0.407 AC: 1409 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		1.3
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: rs222035; hg19: chr4-72621674;