Genetic Variant CPSF7:c.-132_-131delGG (chr11-61429988-GCC-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000394888.8(CPSF7):c.-132_-131delGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,047,148 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CPSF7
ENST00000394888.8 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.35

Publications

4 publications found

Variant links:

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]

CPSF7 links:

ENSG00000256591 (HGNC:):

ENSG00000256591 links:

SDHAF2 (HGNC:26034): (succinate dehydrogenase complex assembly factor 2) This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]

SDHAF2 Gene-Disease associations (from GenCC):

hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
pheochromocytoma/paraganglioma syndrome 2
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

SDHAF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394888.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPSF7	NM_001142565.3	MANE Select	c.-132_-131delGG	upstream_gene	N/A	NP_001136037.1	Q8N684-2
SDHAF2	NM_017841.4	MANE Select	c.-158_-157delCC	upstream_gene	N/A	NP_060311.1	Q9NX18
CPSF7	NM_024811.4		c.-160_-159delGG	upstream_gene	N/A	NP_079087.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CPSF7	ENST00000394888.8	TSL:2	c.-132_-131delGG	5_prime_UTR	Exon 1 of 10	ENSP00000378352.4	Q8N684-1
CPSF7	ENST00000859449.1		c.-132_-131delGG	5_prime_UTR	Exon 1 of 9	ENSP00000529508.1
CPSF7	ENST00000859445.1		c.-56+56_-56+57delGG	intron	N/A	ENSP00000529504.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000105

AC:

AN:

1047148

Hom.:

AF XY:

0.00000954

AC XY:

AN XY:

524192

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000425

AC:

AN:

23506

American (AMR)

AF:

0.00

AC:

AN:

28534

Ashkenazi Jewish (ASJ)

AF:

0.0000521

AC:

AN:

19196

East Asian (EAS)

AF:

0.00

AC:

AN:

33014

South Asian (SAS)

AF:

0.0000156

AC:

AN:

63910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3326

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

793554

Other (OTH)

AF:

0.00

AC:

AN:

46100

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000234906), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.311

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over