4-71745973-G-T

Position:

• chr4-71745973-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000583.4(GC):​c.*25+178C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 151,454 control chromosomes in the GnomAD database, including 80 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 0.027 (80 hom., cov: 27)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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]

GC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0265 (4016/151454) while in subpopulation NFE AF= 0.0392 (2659/67836). AF 95% confidence interval is 0.038. There are 80 homozygotes in gnomad4. There are 1934 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 80 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GC	NM_000583.4	c.*25+178C>A		intron_variant		ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.*25+178C>A		intron_variant			NP_001191236.1
GC	NM_001204306.1	c.*25+178C>A		intron_variant			NP_001191235.1
GC	XM_006714177.3	c.*39+178C>A		intron_variant			XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.*25+178C>A		intron_variant		1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4017 AN: 151336 Hom.: 80 Cov.: 27

Gnomad AFR AF: 0.00744

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0197

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

GnomAD4 genome AF: 0.0265 AC: 4016 AN: 151454 Hom.: 80 Cov.: 27 AF XY: 0.0261 AC XY: 1934 AN XY: 74010

Gnomad4 AFR AF: 0.00742

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0592

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0195

Alfa AF: 0.0193 Hom.: 836

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs842999; hg19: chr4-72611690;