chr5-34025806-G-A

Variant names:

• chr5-34025806-G-A
• rs299602
• NM_181435.6:c.701-1798C>T

Variant summary

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

The NM_181435.6(C1QTNF3):​c.701-1798C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,110 control chromosomes in the GnomAD database, including 13,919 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 0.42 (13919 hom., cov: 33)
• Consequence: C1QTNF3 NM_181435.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 3 publications found

Genes affected

C1QTNF3 (HGNC:14326): (C1q and TNF related 3) Enables identical protein binding activity. Involved in several processes, including cellular triglyceride homeostasis; negative regulation of NIK/NF-kappaB signaling; and regulation of cytokine production. Acts upstream of or within negative regulation of gluconeogenesis. Located in extracellular exosome and membrane. [provided by Alliance of Genome Resources, Apr 2022]

C1QTNF3-AMACR (HGNC:49198): (C1QTNF3-AMACR readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C1q and tumor necrosis factor related protein 3 (C1QTNF3) and alpha-methylacyl-CoA racemase (AMACR) genes on chromosome 5. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not likely to produce a protein product. [provided by RefSeq, Mar 2011]

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 (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181435.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF3	NM_181435.6	MANE Select	c.701-1798C>T		intron	N/A	NP_852100.3
	C1QTNF3	NM_030945.4		c.482-1798C>T		intron	N/A	NP_112207.1
	C1QTNF3-AMACR	NR_037951.1		n.509-1798C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QTNF3	ENST00000382065.8	TSL:1 MANE Select	c.701-1798C>T		intron	N/A	ENSP00000371497.3
	C1QTNF3	ENST00000231338.7	TSL:1	c.482-1798C>T		intron	N/A	ENSP00000231338.7
	C1QTNF3-AMACR	ENST00000382079.3	TSL:2	n.434-1798C>T		intron	N/A	ENSP00000371511.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63092 AN: 151990 Hom.: 13885 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.415 AC: 63176 AN: 152110 Hom.: 13919 Cov.: 33 AF XY: 0.418 AC XY: 31089 AN XY: 74370

African (AFR) AF: 0.539 AC: 22347 AN: 41458

American (AMR) AF: 0.413 AC: 6320 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2507 AN: 5176

South Asian (SAS) AF: 0.652 AC: 3145 AN: 4822

European-Finnish (FIN) AF: 0.296 AC: 3135 AN: 10580

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22983 AN: 67992

Other (OTH) AF: 0.455 AC: 962 AN: 2114

Alfa AF: 0.387 Hom.: 1548

Bravo AF: 0.426

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.33
PhyloP100		-0.21
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: rs299602; hg19: chr5-34025911;