4-71751215-G-A

Variant names:

• chr4-71751215-G-A
• rs222040
• NM_000583.4:c.1395+1303C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 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.1395+1303C>T		intron	N/A	NP_000574.2
	GC	NM_001204307.1		c.1452+1303C>T		intron	N/A	NP_001191236.1
	GC	NM_001204306.1		c.1395+1303C>T		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.1395+1303C>T		intron	N/A	ENSP00000273951.8
	GC	ENST00000504199.5	TSL:1	c.1452+1303C>T		intron	N/A	ENSP00000421725.1
	GC	ENST00000513476.5	TSL:5	c.1395+1303C>T		intron	N/A	ENSP00000426683.1

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

African (AFR) AF: 0.418 AC: 17315 AN: 41450

American (AMR) AF: 0.584 AC: 8910 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.370 AC: 1904 AN: 5146

South Asian (SAS) AF: 0.556 AC: 2681 AN: 4822

European-Finnish (FIN) AF: 0.756 AC: 7991 AN: 10570

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38721 AN: 67962

Other (OTH) AF: 0.545 AC: 1149 AN: 2110

Alfa AF: 0.560 Hom.: 5025

Bravo AF: 0.515

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.79
DANN	Benign	0.35
PhyloP100		0.0030
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: rs222040; hg19: chr4-72616932;