rs2291134

Positions:

• chr8-144400142-C-A
• chr8-144400142-C-G
• chr8-144400142-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013291.3(CPSF1):​c.937+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0000079 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000012 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPSF1 NM_013291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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]

MIR1234 (HGNC:33926): (microRNA 1234) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.18).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPSF1	NM_013291.3	c.937+24G>T		intron_variant		ENST00000616140.2
MIR1234	NR_031600.2	n.24G>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPSF1	ENST00000616140.2	c.937+24G>T		intron_variant		1	NM_013291.3	P1
MIR1234	ENST00000579254.1	n.24G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 127252 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000186

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000125 AC: 14 AN: 1120950 Hom.: 2 Cov.: 19 AF XY: 0.00000897 AC XY: 5 AN XY: 557452

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000166

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000786 AC: 1 AN: 127252 Hom.: 0 Cov.: 26 AF XY: 0.0000161 AC XY: 1 AN XY: 62140

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000186

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2291134; hg19: -;