rs3733359

Variant names:

• chr4-71784057-G-A
• rs3733359
• NM_000583.4:c.-39C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-71784057-G-A
• chr4-71784057-G-C
• chr4-71784057-G-T

Variant summary

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

The NM_001204307.1(GC):​c.22-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 1,586,812 control chromosomes in the GnomAD database, including 9,246 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1866 hom., cov: 32)
  • Exomes 𝑓: 0.079 (7380 hom.)
• Consequence: GC NM_001204307.1 splice_region, intron
• Scores: Splicing: ADA: 0.0003753
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 47 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	NM_000583.4	MANE Select	c.-39C>T		5_prime_UTR	Exon 1 of 13	NP_000574.2
	GC	NM_001440458.1		c.-39C>T		5_prime_UTR	Exon 1 of 12	NP_001427387.1
	GC	NM_001204307.1		c.22-3C>T		splice_region intron	N/A	NP_001191236.1	P02774-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GC	ENST00000273951.13	TSL:1 MANE Select	c.-39C>T		5_prime_UTR	Exon 1 of 13	ENSP00000273951.8	P02774-1
	GC	ENST00000504199.5	TSL:1	c.22-3C>T		splice_region intron	N/A	ENSP00000421725.1	P02774-3
	GC	ENST00000882425.1		c.-39C>T		5_prime_UTR	Exon 1 of 13	ENSP00000552484.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19384 AN: 151372 Hom.: 1859 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0955

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.122 AC: 28747 AN: 236118 AF XY: 0.114

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.0936

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0980

GnomAD4 exome AF: 0.0791 AC: 113497 AN: 1435320 Hom.: 7380 Cov.: 27 AF XY: 0.0796 AC XY: 56804 AN XY: 713592

African (AFR) AF: 0.247 AC: 8013 AN: 32392

American (AMR) AF: 0.173 AC: 7218 AN: 41664

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 2297 AN: 25304

East Asian (EAS) AF: 0.348 AC: 13628 AN: 39156

South Asian (SAS) AF: 0.128 AC: 10394 AN: 81394

European-Finnish (FIN) AF: 0.0348 AC: 1839 AN: 52906

Middle Eastern (MID) AF: 0.114 AC: 647 AN: 5662

European-Non Finnish (NFE) AF: 0.0578 AC: 63499 AN: 1097738

Other (OTH) AF: 0.101 AC: 5962 AN: 59104

GnomAD4 genome AF: 0.128 AC: 19420 AN: 151492 Hom.: 1866 Cov.: 32 AF XY: 0.126 AC XY: 9352 AN XY: 74016

African (AFR) AF: 0.239 AC: 9882 AN: 41328

American (AMR) AF: 0.124 AC: 1877 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.0955 AC: 330 AN: 3454

East Asian (EAS) AF: 0.386 AC: 1970 AN: 5100

South Asian (SAS) AF: 0.123 AC: 593 AN: 4806

European-Finnish (FIN) AF: 0.0323 AC: 342 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4044 AN: 67716

Other (OTH) AF: 0.124 AC: 262 AN: 2106

Alfa AF: 0.0858 Hom.: 3668

Bravo AF: 0.144

Asia WGS AF: 0.251 AC: 872 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.32
PhyloP100		1.4
PromoterAI		-0.061	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00038
dbscSNV1_RF	Benign	0.0020
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: rs3733359; hg19: chr4-72649774; COSMIC: COSV56738424; COSMIC: COSV56738424;