8-144393732-C-T

Variant names:

• chr8-144393732-C-T
• rs118182362
• NM_013291.3:c.4080G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_013291.3(CPSF1):​c.4080G>A​(p.Leu1360Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,575,046 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (2 hom.)
• Consequence: CPSF1 NM_013291.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.327
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 8-144393732-C-T is Benign according to our data. Variant chr8-144393732-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.327 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00107 (163/152204) while in subpopulation NFE AF = 0.00169 (115/67980). AF 95% confidence interval is 0.00144. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 163 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF1	NM_013291.3	MANE Select	c.4080G>A	p.Leu1360Leu	synonymous	Exon 36 of 38	NP_037423.2	Q10570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF1	ENST00000616140.2	TSL:1 MANE Select	c.4080G>A	p.Leu1360Leu	synonymous	Exon 36 of 38	ENSP00000484669.1	Q10570
	CPSF1	ENST00000620219.4	TSL:1	c.4080G>A	p.Leu1360Leu	synonymous	Exon 35 of 37	ENSP00000478145.1	Q10570
	CPSF1	ENST00000886816.1		c.4104G>A	p.Leu1368Leu	synonymous	Exon 36 of 38	ENSP00000556875.1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00133 AC: 256 AN: 192992 AF XY: 0.00128

Gnomad AFR exome AF: 0.000172

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00103

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00188 AC: 2674 AN: 1422842 Hom.: 2 Cov.: 59 AF XY: 0.00181 AC XY: 1275 AN XY: 705842

African (AFR) AF: 0.000332 AC: 11 AN: 33170

American (AMR) AF: 0.00154 AC: 61 AN: 39548

Ashkenazi Jewish (ASJ) AF: 0.0000783 AC: 2 AN: 25554

East Asian (EAS) AF: 0.00 AC: 0 AN: 38442

South Asian (SAS) AF: 0.000931 AC: 77 AN: 82664

European-Finnish (FIN) AF: 0.00114 AC: 45 AN: 39516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00218 AC: 2392 AN: 1099020

Other (OTH) AF: 0.00145 AC: 86 AN: 59218

GnomAD4 genome AF: 0.00107 AC: 163 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.00105 AC XY: 78 AN XY: 74410

African (AFR) AF: 0.000289 AC: 12 AN: 41514

American (AMR) AF: 0.00157 AC: 24 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00169 AC: 115 AN: 67980

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00110

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.9
DANN	Benign	0.91
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs118182362; hg19: chr8-145618947;