chr5-34044390-G-C

Variant names:

• chr5-34044390-G-C
• rs299616
• ENST00000382079.3:n.37-8632C>G

Variant summary

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

The ENST00000382079.3(C1QTNF3-AMACR):​n.37-8632C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,176 control chromosomes in the GnomAD database, including 1,588 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 0.14 (1588 hom., cov: 32)
• Consequence: C1QTNF3-AMACR ENST00000382079.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 2 publications found

Genes affected

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QTNF3-AMACR	NR_037951.1	n.112-8632C>G		intron_variant	Intron 1 of 8
C1QTNF3	NR_146599.1	n.895-8632C>G		intron_variant	Intron 7 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QTNF3-AMACR	ENST00000382079.3	n.37-8632C>G		intron_variant	Intron 1 of 8	2		ENSP00000371511.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21149 AN: 152058 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.139 AC: 21176 AN: 152176 Hom.: 1588 Cov.: 32 AF XY: 0.143 AC XY: 10633 AN XY: 74400

African (AFR) AF: 0.0820 AC: 3407 AN: 41524

American (AMR) AF: 0.169 AC: 2577 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1279 AN: 5166

South Asian (SAS) AF: 0.239 AC: 1150 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9801 AN: 68016

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.0605 Hom.: 67

Bravo AF: 0.138

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		0.12

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: rs299616; hg19: chr5-34044495;