rs201600135

Variant names:

• chr5-57246405-C-A
• NM_022913.4:c.584C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-57246405-C-A
• chr5-57246405-C-G
• chr5-57246405-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022913.4(GPBP1):​c.584C>A​(p.Pro195Gln) variant causes a missense 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. 15/21 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. P195L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPBP1 NM_022913.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051724344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPBP1	NM_022913.4	c.584C>A	p.Pro195Gln	missense_variant	Exon 7 of 12	ENST00000506184.7	NP_075064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPBP1	ENST00000506184.7	c.584C>A	p.Pro195Gln	missense_variant	Exon 7 of 12	1	NM_022913.4	ENSP00000421202.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.017	.;.;T;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.59	T;T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.052	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.090	.;.;N;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.20	N;N;N;N;N
REVEL	Benign	0.038
Sift	Benign	0.78	T;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T
Polyphen		0.0	B;.;B;B;B
Vest4		0.25
MutPred		0.18		Gain of sheet (P = 0.0477);.;.;.;.;
MVP		0.043
MPC		0.32
ClinPred		0.28	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-56542232;