chr8-144405804-A-C

Variant names:

• chr8-144405804-A-C
• rs13258200
• NM_013291.3:c.144+3211T>G

Variant summary

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

The NM_013291.3(CPSF1):​c.144+3211T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,930 control chromosomes in the GnomAD database, including 11,604 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 0.38 (11604 hom., cov: 31)
• Consequence: CPSF1 NM_013291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• Publications: 19 publications found

Genes affected

CPSF1 (HGNC:2324): (cleavage and polyadenylation specific factor 1) Cleavage and polyadenylation specificity factor (CPSF) is a multisubunit complex that plays a central role in 3-prime processing of pre-mRNAs. CPSF recognizes the AAUAAA signal in the pre-mRNA and interacts with other proteins to facilitate both RNA cleavage and poly(A) synthesis. CPSF1 is the largest subunit of the CPSF complex (Murthy and Manley, 1995 [PubMed 7590244]).[supplied by OMIM, Mar 2008]

CPSF1 Gene-Disease associations (from GenCC):

• myopia 27

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013291.3. 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
	CPSF1	NM_013291.3	MANE Select	c.144+3211T>G		intron	N/A	NP_037423.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF1	ENST00000616140.2	TSL:1 MANE Select	c.144+3211T>G		intron	N/A	ENSP00000484669.1
	CPSF1	ENST00000620219.4	TSL:1	c.144+3211T>G		intron	N/A	ENSP00000478145.1
	CPSF1	ENST00000531042.5	TSL:5	n.144+3211T>G		intron	N/A	ENSP00000435761.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58108 AN: 151814 Hom.: 11596 Cov.: 31

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.383 AC: 58148 AN: 151930 Hom.: 11604 Cov.: 31 AF XY: 0.389 AC XY: 28887 AN XY: 74288

African (AFR) AF: 0.347 AC: 14368 AN: 41420

American (AMR) AF: 0.471 AC: 7189 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1203 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3330 AN: 5162

South Asian (SAS) AF: 0.588 AC: 2832 AN: 4820

European-Finnish (FIN) AF: 0.382 AC: 4034 AN: 10570

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23940 AN: 67922

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.367 Hom.: 6427

Bravo AF: 0.389

Asia WGS AF: 0.570 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.87
PhyloP100		0.69
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: rs13258200; hg19: chr8-145631197;