chr5-34034708-C-G

Variant names:

• chr5-34034708-C-G
• rs213583
• NM_181435.6:c.415+939G>C

Variant summary

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

The NM_181435.6(C1QTNF3):​c.415+939G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,008 control chromosomes in the GnomAD database, including 17,033 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 0.45 (17033 hom., cov: 32)
• Consequence: C1QTNF3 NM_181435.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF3	NM_181435.6	c.415+939G>C		intron_variant	Intron 2 of 5	ENST00000382065.8	NP_852100.3
C1QTNF3	NM_030945.4	c.196+939G>C		intron_variant	Intron 2 of 5		NP_112207.1
C1QTNF3-AMACR	NR_037951.1	n.223+939G>C		intron_variant	Intron 2 of 8
C1QTNF3	NR_146599.1	n.1006+939G>C		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF3	ENST00000382065.8	c.415+939G>C		intron_variant	Intron 2 of 5	1	NM_181435.6	ENSP00000371497.3
C1QTNF3	ENST00000231338.7	c.196+939G>C		intron_variant	Intron 2 of 5	1		ENSP00000231338.7
C1QTNF3-AMACR	ENST00000382079.3	n.148+939G>C		intron_variant	Intron 2 of 8	2		ENSP00000371511.3
C1QTNF3	ENST00000508434.1	n.283+939G>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68777 AN: 151890 Hom.: 16992 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.453 AC: 68873 AN: 152008 Hom.: 17033 Cov.: 32 AF XY: 0.456 AC XY: 33868 AN XY: 74272

African (AFR) AF: 0.628 AC: 26013 AN: 41412

American (AMR) AF: 0.437 AC: 6680 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1393 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2631 AN: 5160

South Asian (SAS) AF: 0.735 AC: 3548 AN: 4826

European-Finnish (FIN) AF: 0.297 AC: 3142 AN: 10574

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23889 AN: 67984

Other (OTH) AF: 0.501 AC: 1056 AN: 2108

Alfa AF: 0.394 Hom.: 1536

Bravo AF: 0.467

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.75
PhyloP100		-2.3
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: rs213583; hg19: chr5-34034813;