ENST00000340437.8:c.67C>A

Variant names:

• chr11-61429764-G-T
• rs538551317
• ENST00000340437.8:c.67C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000340437.8(CPSF7):​c.67C>A​(p.Arg23Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,390,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CPSF7 ENST00000340437.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 0 publications found

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:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=0.866 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340437.8. 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
	CPSF7	NM_001142565.3	MANE Select	c.-56+150C>A		intron	N/A	NP_001136037.1	Q8N684-2
	CPSF7	NM_024811.4		c.67C>A	p.Arg23Arg	synonymous	Exon 1 of 10	NP_079087.3
	CPSF7	NM_001136040.4		c.-56+150C>A		intron	N/A	NP_001129512.1	Q8N684-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF7	ENST00000340437.8	TSL:1	c.67C>A	p.Arg23Arg	synonymous	Exon 1 of 10	ENSP00000345412.4	Q8N684-3
	CPSF7	ENST00000439958.8	TSL:1 MANE Select	c.-56+150C>A		intron	N/A	ENSP00000397203.3	Q8N684-2
	CPSF7	ENST00000413232.5	TSL:3	c.-63C>A		5_prime_UTR	Exon 1 of 6	ENSP00000393828.1	J3QT54

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390542 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 685876

African (AFR) AF: 0.00 AC: 0 AN: 31206

American (AMR) AF: 0.00 AC: 0 AN: 35324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24988

East Asian (EAS) AF: 0.00 AC: 0 AN: 35218

South Asian (SAS) AF: 0.00 AC: 0 AN: 78480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076412

Other (OTH) AF: 0.00 AC: 0 AN: 57730

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.87
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

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: rs538551317; hg19: chr11-61197236;