NM_001161346.2:c.584-3560G>A

Variant names:

• chr12-132865194-C-T
• rs11610954
• NM_001161346.2:c.584-3560G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CHFR	NM_001161346.2	c.584-3560G>A		intron_variant	Intron 6 of 17	ENST00000450056.7	NP_001154818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHFR	ENST00000450056.7	c.584-3560G>A		intron_variant	Intron 6 of 17	2	NM_001161346.2	ENSP00000398735.2
CHFR	ENST00000315585.11	n.20-3560G>A		intron_variant	Intron 4 of 15	2		ENSP00000320557.8

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

African (AFR) AF: 0.0141 AC: 584 AN: 41544

American (AMR) AF: 0.0531 AC: 812 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3472

East Asian (EAS) AF: 0.135 AC: 697 AN: 5166

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4826

European-Finnish (FIN) AF: 0.0452 AC: 478 AN: 10584

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0835 AC: 5679 AN: 68000

Other (OTH) AF: 0.0579 AC: 122 AN: 2108

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
PhyloP100		-0.96
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: rs11610954; hg19: chr12-133441780;