chr12-69273295-T-A

Variant names:

• chr12-69273295-T-A
• rs1463335
• NM_007007.3:c.*3787T>A

Variant summary

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

The NM_007007.3(CPSF6):​c.*3787T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 349,128 control chromosomes in the GnomAD database, including 56,494 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 0.55 (23143 hom., cov: 31)
  • Exomes 𝑓: 0.57 (33351 hom.)
• Consequence: CPSF6 NM_007007.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 13 publications found

Genes affected

CPSF6 (HGNC:13871): (cleavage and polyadenylation specific factor 6) The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. The cleavage factor complex is composed of four polypeptides. This gene encodes the 68kD subunit. It has a domain organization reminiscent of spliceosomal proteins. [provided by RefSeq, Jul 2008]

MIR1279 (HGNC:35357): (microRNA 1279) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007007.3. 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
	CPSF6	NM_007007.3	MANE Select	c.*3787T>A		3_prime_UTR	Exon 10 of 10	NP_008938.2
	CPSF6	NM_001300947.2		c.*3787T>A		3_prime_UTR	Exon 11 of 11	NP_001287876.1
	MIR1279	NR_031692.1		n.-77A>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF6	ENST00000435070.7	TSL:1 MANE Select	c.*3787T>A		3_prime_UTR	Exon 10 of 10	ENSP00000391774.2
	CPSF6	ENST00000650046.1		n.*6107T>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000497420.1
	CPSF6	ENST00000650046.1		n.*6107T>A		3_prime_UTR	Exon 12 of 12	ENSP00000497420.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83271 AN: 151468 Hom.: 23136 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.573 AC: 113104 AN: 197542 Hom.: 33351 Cov.: 0 AF XY: 0.580 AC XY: 66124 AN XY: 113922

African (AFR) AF: 0.524 AC: 2766 AN: 5278

American (AMR) AF: 0.594 AC: 8362 AN: 14080

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 2539 AN: 4926

East Asian (EAS) AF: 0.728 AC: 6888 AN: 9456

South Asian (SAS) AF: 0.673 AC: 24537 AN: 36460

European-Finnish (FIN) AF: 0.440 AC: 6211 AN: 14100

Middle Eastern (MID) AF: 0.480 AC: 1040 AN: 2166

European-Non Finnish (NFE) AF: 0.546 AC: 56031 AN: 102534

Other (OTH) AF: 0.554 AC: 4730 AN: 8542

GnomAD4 genome AF: 0.550 AC: 83315 AN: 151586 Hom.: 23143 Cov.: 31 AF XY: 0.548 AC XY: 40569 AN XY: 74082

African (AFR) AF: 0.537 AC: 22249 AN: 41446

American (AMR) AF: 0.565 AC: 8615 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3765 AN: 5180

South Asian (SAS) AF: 0.683 AC: 3296 AN: 4828

European-Finnish (FIN) AF: 0.431 AC: 4542 AN: 10548

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37313 AN: 67574

Other (OTH) AF: 0.531 AC: 1113 AN: 2096

Alfa AF: 0.554 Hom.: 2854

Bravo AF: 0.554

Asia WGS AF: 0.665 AC: 2310 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.8
DANN	Benign	0.72
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1463335; hg19: chr12-69667075;