chr4-71784057-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001204307.1(GC):​c.22-3C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GC NM_001204307.1 splice_region, intron
• Scores: Splicing: ADA: 0.0003753
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>G		5_prime_UTR	Exon 1 of 13	NP_000574.2
	GC	NM_001440458.1		c.-39C>G		5_prime_UTR	Exon 1 of 12	NP_001427387.1
	GC	NM_001204307.1		c.22-3C>G		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>G		5_prime_UTR	Exon 1 of 13	ENSP00000273951.8	P02774-1
	GC	ENST00000504199.5	TSL:1	c.22-3C>G		splice_region intron	N/A	ENSP00000421725.1	P02774-3
	GC	ENST00000882425.1		c.-39C>G		5_prime_UTR	Exon 1 of 13	ENSP00000552484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.38
PhyloP100		1.4
PromoterAI		0.013	Neutral

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;