rs3786054

Variant names:

• chr17-5435739-G-A
• rs3786054
• NM_001212.4:c.384-773C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-5435739-G-A
• chr17-5435739-G-C
• chr17-5435739-G-T

Variant summary

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

The NM_001212.4(C1QBP):​c.384-773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 151,826 control chromosomes in the GnomAD database, including 4,148 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 0.20 (4148 hom., cov: 30)
• Consequence: C1QBP NM_001212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 15 publications found

Genes affected

C1QBP (HGNC:1243): (complement C1q binding protein) The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein. [provided by RefSeq, Jul 2008]

C1QBP Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 33

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QBP	NM_001212.4	c.384-773C>T		intron_variant	Intron 2 of 5	ENST00000225698.8	NP_001203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QBP	ENST00000225698.8	c.384-773C>T		intron_variant	Intron 2 of 5	1	NM_001212.4	ENSP00000225698.4
C1QBP	ENST00000574444.5	c.72-773C>T		intron_variant	Intron 2 of 5	3		ENSP00000460308.1
C1QBP	ENST00000570805.1	c.72-773C>T		intron_variant	Intron 2 of 5	3		ENSP00000460638.1
C1QBP	ENST00000573406.1	n.466-773C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30487 AN: 151708 Hom.: 4152 Cov.: 30

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.201 AC: 30495 AN: 151826 Hom.: 4148 Cov.: 30 AF XY: 0.211 AC XY: 15624 AN XY: 74180

African (AFR) AF: 0.0748 AC: 3097 AN: 41424

American (AMR) AF: 0.244 AC: 3719 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3342 AN: 5144

South Asian (SAS) AF: 0.362 AC: 1737 AN: 4796

European-Finnish (FIN) AF: 0.322 AC: 3391 AN: 10522

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13933 AN: 67926

Other (OTH) AF: 0.214 AC: 447 AN: 2092

Alfa AF: 0.202 Hom.: 1216

Bravo AF: 0.190

Asia WGS AF: 0.491 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.38
PhyloP100		0.24
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: rs3786054; hg19: chr17-5339059;