4-71777771-T-C

Variant names:

• chr4-71777771-T-C
• rs1155563
• NM_000583.4:c.58+6190A>G

Variant summary

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

The NM_000583.4(GC):​c.58+6190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,114 control chromosomes in the GnomAD database, including 4,385 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 0.22 (4385 hom., cov: 29)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 109 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000583.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_000583.4	MANE Select	c.58+6190A>G		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.115+6190A>G		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.58+6190A>G		intron	N/A	NP_001191235.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000273951.13	TSL:1 MANE Select	c.58+6190A>G		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.115+6190A>G		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.58+6190A>G		intron	N/A	ENSP00000426683.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 33932 AN: 150996 Hom.: 4383 Cov.: 29

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.225 AC: 33945 AN: 151114 Hom.: 4385 Cov.: 29 AF XY: 0.222 AC XY: 16347 AN XY: 73730

African (AFR) AF: 0.101 AC: 4144 AN: 41228

American (AMR) AF: 0.220 AC: 3322 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 903 AN: 3456

East Asian (EAS) AF: 0.339 AC: 1724 AN: 5084

South Asian (SAS) AF: 0.292 AC: 1392 AN: 4766

European-Finnish (FIN) AF: 0.204 AC: 2135 AN: 10482

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19436 AN: 67732

Other (OTH) AF: 0.234 AC: 489 AN: 2092

Alfa AF: 0.273 Hom.: 11814

Bravo AF: 0.221

Asia WGS AF: 0.253 AC: 883 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.12
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: rs1155563; hg19: chr4-72643488;