chr12-69275445-G-A

Variant names:

• chr12-69275445-G-A
• rs998022
• ENST00000927154.1:c.*4-3779G>A

Variant summary

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

The ENST00000927154.1(CPSF6):​c.*4-3779G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,032 control chromosomes in the GnomAD database, including 17,885 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 0.48 (17885 hom., cov: 32)
• Consequence: CPSF6 ENST00000927154.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 8 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]

CPSF6 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000927154.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF6	ENST00000927154.1		c.*4-3779G>A		intron	N/A	ENSP00000597213.1
	CPSF6	ENST00000941456.1		c.*4-3779G>A		intron	N/A	ENSP00000611515.1
	CPSF6	ENST00000886656.1		c.*4-3779G>A		intron	N/A	ENSP00000556715.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73658 AN: 151914 Hom.: 17878 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.485 AC: 73689 AN: 152032 Hom.: 17885 Cov.: 32 AF XY: 0.478 AC XY: 35503 AN XY: 74298

African (AFR) AF: 0.513 AC: 21252 AN: 41438

American (AMR) AF: 0.463 AC: 7066 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2241 AN: 5176

South Asian (SAS) AF: 0.393 AC: 1899 AN: 4826

European-Finnish (FIN) AF: 0.400 AC: 4221 AN: 10558

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33908 AN: 67988

Other (OTH) AF: 0.463 AC: 977 AN: 2108

Alfa AF: 0.490 Hom.: 9257

Bravo AF: 0.489

Asia WGS AF: 0.352 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.22
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs998022; hg19: chr12-69669225;