ENST00000394888.8:c.-132_-131delGG

Variant names:

• chr11-61429988-GCC-G
• rs34378918
• ENST00000394888.8:c.-132_-131delGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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]

ENSG00000256591 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF7	NM_001142565.3	c.-132_-131delGG		upstream_gene_variant		ENST00000439958.8	NP_001136037.1
SDHAF2	NM_017841.4	c.-158_-157delCC		upstream_gene_variant		ENST00000301761.7	NP_060311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF7	ENST00000439958.8	c.-132_-131delGG		upstream_gene_variant		1	NM_001142565.3	ENSP00000397203.3
SDHAF2	ENST00000301761.7	c.-158_-157delCC		upstream_gene_variant		1	NM_017841.4	ENSP00000301761.3
ENSG00000256591	ENST00000541135.5	c.-158_-157delCC		upstream_gene_variant		4		ENSP00000443130.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000105 AC: 11 AN: 1047148 Hom.: 0 AF XY: 0.00000954 AC XY: 5 AN XY: 524192

Gnomad4 AFR exome AF: 0.0000425

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000521

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000156

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs34378918; hg19: chr11-61197460;