11-61415916-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142565.3(CPSF7):c.939-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 846,474 control chromosomes in the GnomAD database, including 7,081 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 0.096 (915 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6166 hom.)
• Consequence: CPSF7 NM_001142565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

Genes affected

CPSF7 (HGNC:30098): (cleavage and polyadenylation specific factor 7) Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPSF7	NM_001142565.3	c.939-132G>A		intron_variant		ENST00000439958.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPSF7	ENST00000439958.8	c.939-132G>A		intron_variant		1	NM_001142565.3	P4

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14685 AN: 152072 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.125 AC: 86763 AN: 694284 Hom.: 6166 Cov.: 9 AF XY: 0.127 AC XY: 45693 AN XY: 359514

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.0559

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0965 AC: 14685 AN: 152190 Hom.: 915 Cov.: 32 AF XY: 0.0967 AC XY: 7199 AN XY: 74418

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0988

Alfa AF: 0.123 Hom.: 1770

Bravo AF: 0.0856

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.23
Dann	Benign	0.41

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: rs17704641; hg19: chr11-61183388;