rs222040

Positions:

• chr4-71751215-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000583.4(GC):​c.1395+1303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,000 control chromosomes in the GnomAD database, including 22,504 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 0.54 (22504 hom., cov: 32)
• Consequence: GC NM_000583.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GC	NM_000583.4	c.1395+1303C>T		intron_variant		ENST00000273951.13
GC	NM_001204306.1	c.1395+1303C>T		intron_variant
GC	NM_001204307.1	c.1452+1303C>T		intron_variant
GC	XM_006714177.3	c.1262+3196C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GC	ENST00000273951.13	c.1395+1303C>T		intron_variant		1	NM_000583.4	P1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81393 AN: 151880 Hom.: 22508 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.536 AC: 81411 AN: 152000 Hom.: 22504 Cov.: 32 AF XY: 0.546 AC XY: 40556 AN XY: 74280

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.545

Alfa AF: 0.563 Hom.: 4954

Bravo AF: 0.515

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.79
DANN	Benign	0.35

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: rs222040; hg19: chr4-72616932;