rs11610954

chr12-132865194-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161346.2(CHFR):c.584-3560G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,188 control chromosomes in the GnomAD database, including 375 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 0.060 (375 hom., cov: 32)
• Consequence: CHFR NM_001161346.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

Genes affected

CHFR (HGNC:20455): (checkpoint with forkhead and ring finger domains) This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHFR	NM_001161346.2	c.584-3560G>A		intron_variant		ENST00000450056.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHFR	ENST00000450056.7	c.584-3560G>A		intron_variant		2	NM_001161346.2

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9147 AN: 152070 Hom.: 374 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0601 AC: 9151 AN: 152188 Hom.: 375 Cov.: 32 AF XY: 0.0588 AC XY: 4373 AN XY: 74380

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0524

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0646 Hom.: 50

Bravo AF: 0.0590

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.4
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs11610954; hg19: chr12-133441780;