4-71789160-G-T

Variant names:

• chr4-71789160-G-T
• rs705125
• ENST00000504199.5:c.22-5106C>A

Variant summary

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

The ENST00000504199.5(GC):​c.22-5106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,478 control chromosomes in the GnomAD database, including 38,069 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 0.69 (38069 hom., cov: 30)
• Consequence: GC ENST00000504199.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_001204307.1	c.22-5106C>A		intron_variant	Intron 1 of 13		NP_001191236.1
GC	NM_001204306.1	c.-36-5106C>A		intron_variant	Intron 1 of 13		NP_001191235.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000504199.5	c.22-5106C>A		intron_variant	Intron 1 of 13	1		ENSP00000421725.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 103947 AN: 151360 Hom.: 38066 Cov.: 30

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.686 AC: 103971 AN: 151478 Hom.: 38069 Cov.: 30 AF XY: 0.689 AC XY: 51027 AN XY: 74018

African (AFR) AF: 0.407 AC: 16808 AN: 41290

American (AMR) AF: 0.780 AC: 11842 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2907 AN: 3462

East Asian (EAS) AF: 0.610 AC: 3118 AN: 5114

South Asian (SAS) AF: 0.827 AC: 3983 AN: 4818

European-Finnish (FIN) AF: 0.772 AC: 8122 AN: 10520

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.808 AC: 54767 AN: 67780

Other (OTH) AF: 0.712 AC: 1500 AN: 2106

Alfa AF: 0.727 Hom.: 5244

Bravo AF: 0.669

Asia WGS AF: 0.690 AC: 2365 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.13
PhyloP100		-0.010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs705125; hg19: chr4-72654877;