4-71767214-C-T

Variant names:

• chr4-71767214-C-T
• rs222014
• NM_000583.4:c.261+1087G>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.261+1087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,050 control chromosomes in the GnomAD database, including 701 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 0.090 (701 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.261+1087G>A		intron_variant	Intron 3 of 12	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.318+1087G>A		intron_variant	Intron 4 of 13		NP_001191236.1
GC	NM_001204306.1	c.261+1087G>A		intron_variant	Intron 4 of 13		NP_001191235.1
GC	NM_001440458.1	c.261+1087G>A		intron_variant	Intron 3 of 11		NP_001427387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.261+1087G>A		intron_variant	Intron 3 of 12	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13646 AN: 151934 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0898 AC: 13659 AN: 152050 Hom.: 701 Cov.: 32 AF XY: 0.0921 AC XY: 6844 AN XY: 74300

African (AFR) AF: 0.0818 AC: 3397 AN: 41510

American (AMR) AF: 0.0496 AC: 757 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0374 AC: 180 AN: 4810

European-Finnish (FIN) AF: 0.185 AC: 1956 AN: 10554

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6963 AN: 67954

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0962 Hom.: 403

Bravo AF: 0.0815

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.56
PhyloP100		-0.76
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: rs222014; hg19: chr4-72632931;