chr10-6322791-G-A

Variant names:

• chr10-6322791-G-A
• rs12779447
• ENST00000399868.2:n.122-3755G>A

Variant summary

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

The ENST00000399868.2(LINC02649):​n.122-3755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,202 control chromosomes in the GnomAD database, including 1,651 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 (1651 hom., cov: 32)
• Consequence: LINC02649 ENST00000399868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 4 publications found

Genes affected

LINC02649 (HGNC:54134): (long intergenic non-protein coding RNA 2649)

PFKFB3 (HGNC:8874): (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) The protein encoded by this gene belongs to a family of bifunctional proteins that are involved in both the synthesis and degradation of fructose-2,6-bisphosphate, a regulatory molecule that controls glycolysis in eukaryotes. The encoded protein has a 6-phosphofructo-2-kinase activity that catalyzes the synthesis of fructose-2,6-bisphosphate (F2,6BP), and a fructose-2,6-biphosphatase activity that catalyzes the degradation of F2,6BP. This protein is required for cell cycle progression and prevention of apoptosis. It functions as a regulator of cyclin-dependent kinase 1, linking glucose metabolism to cell proliferation and survival in tumor cells. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

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 (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399868.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02649	ENST00000399868.2	TSL:2	n.122-3755G>A		intron	N/A
	LINC02649	ENST00000659311.1		n.100-3755G>A		intron	N/A
	LINC02649	ENST00000670683.2		n.146-3755G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21606 AN: 152084 Hom.: 1652 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0167

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.142 AC: 21607 AN: 152202 Hom.: 1651 Cov.: 32 AF XY: 0.138 AC XY: 10287 AN XY: 74412

African (AFR) AF: 0.112 AC: 4666 AN: 41528

American (AMR) AF: 0.107 AC: 1637 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3470

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5192

South Asian (SAS) AF: 0.0812 AC: 391 AN: 4818

European-Finnish (FIN) AF: 0.143 AC: 1515 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12425 AN: 68014

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.165 Hom.: 6703

Bravo AF: 0.137

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.75
PhyloP100		0.0080

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12779447; hg19: chr10-6364754;