5-57249559-C-G

Variant names:

• chr5-57249559-C-G
• rs138655196
• NM_022913.4:c.955C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022913.4(GPBP1):​c.955C>G​(p.Arg319Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R319H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPBP1 NM_022913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 4 publications found

Genes affected

GPBP1 (HGNC:29520): (GC-rich promoter binding protein 1) This gene was originally isolated by subtractive hybridization of cDNAs expressed in atherosclerotic plaques with a thrombus, and was found to be expressed only in vascular smooth muscle cells. However, a shorter splice variant was found to be more ubiquitously expressed. This protein is suggested to play a role in the development of atherosclerosis. Studies in mice suggest that it may also function as a GC-rich promoter-specific trans-activating transcription factor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070862025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022913.4. 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
	GPBP1	NM_022913.4	MANE Select	c.955C>G	p.Arg319Gly	missense	Exon 9 of 12	NP_075064.1	Q86WP2-1
	GPBP1	NM_001331037.2		c.1015C>G	p.Arg339Gly	missense	Exon 10 of 13	NP_001317966.1	D4PHA4
	GPBP1	NM_001127236.2		c.976C>G	p.Arg326Gly	missense	Exon 8 of 11	NP_001120708.1	Q86WP2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPBP1	ENST00000506184.7	TSL:1 MANE Select	c.955C>G	p.Arg319Gly	missense	Exon 9 of 12	ENSP00000421202.2	Q86WP2-1
	GPBP1	ENST00000264779.6	TSL:1	c.976C>G	p.Arg326Gly	missense	Exon 8 of 11	ENSP00000264779.6	Q86WP2-2
	GPBP1	ENST00000514387.6	TSL:1	c.442C>G	p.Arg148Gly	missense	Exon 8 of 11	ENSP00000421709.2	Q86WP2-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000840 AC: 2 AN: 238148 AF XY: 0.00000776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000656

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449764 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720972

African (AFR) AF: 0.00 AC: 0 AN: 32798

American (AMR) AF: 0.0000488 AC: 2 AN: 40960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25440

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.00 AC: 0 AN: 83554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108842

Other (OTH) AF: 0.00 AC: 0 AN: 59866

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.038
Sift	Benign	0.15	T
Sift4G	Benign	0.35	T
Polyphen		0.028	B
Vest4		0.26
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.043
MPC		0.47
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.41
Mutation Taster		=94/6	polymorphism

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: rs138655196; hg19: chr5-56545386;