chr12-69273295-T-A

Position:

• chr12-69273295-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPSF6	NM_007007.3	c.*3787T>A		3_prime_UTR_variant	10/10	ENST00000435070.7
CPSF6	NM_001300947.2	c.*3787T>A		3_prime_UTR_variant	11/11
CPSF6	XM_005268588.4	c.*3787T>A		3_prime_UTR_variant	11/11
CPSF6	XM_005268590.4	c.*3787T>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPSF6	ENST00000435070.7	c.*3787T>A		3_prime_UTR_variant	10/10	1	NM_007007.3	A1
CPSF6	ENST00000650046.1	c.*6107T>A		3_prime_UTR_variant, NMD_transcript_variant	12/12

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

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.594

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.554

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

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.531

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.8
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1463335; hg19: chr12-69667075;