chr14-92170369-A-T

Variant names:

• chr14-92170369-A-T
• rs1009170
• NM_017437.3:c.*8625A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017437.3(CPSF2):​c.*8625A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,924 control chromosomes in the GnomAD database, including 7,428 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 0.30 (7428 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CPSF2 NM_017437.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 17 publications found

Genes affected

CPSF2 (HGNC:2325): (cleavage and polyadenylation specific factor 2) Predicted to enable RNA binding activity. Involved in mRNA 3'-end processing by stem-loop binding activity and cleavage. Located in membrane. Part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF2	NM_017437.3	c.*8625A>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000298875.9	NP_059133.1
CPSF2	NM_001322272.2	c.*8625A>T		3_prime_UTR_variant	Exon 16 of 16		NP_001309201.1
CPSF2	NM_001322270.2	c.*8625A>T		3_prime_UTR_variant	Exon 15 of 15		NP_001309199.1
CPSF2	NM_001322271.2	c.*8625A>T		3_prime_UTR_variant	Exon 15 of 15		NP_001309200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF2	ENST00000298875.9	c.*8625A>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_017437.3	ENSP00000298875.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45775 AN: 151806 Hom.: 7401 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.296

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.302 AC: 45841 AN: 151924 Hom.: 7428 Cov.: 32 AF XY: 0.303 AC XY: 22486 AN XY: 74268

African (AFR) AF: 0.416 AC: 17216 AN: 41406

American (AMR) AF: 0.252 AC: 3842 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3464

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5162

South Asian (SAS) AF: 0.351 AC: 1688 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2302 AN: 10556

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16249 AN: 67970

Other (OTH) AF: 0.307 AC: 644 AN: 2100

Alfa AF: 0.270 Hom.: 810

Bravo AF: 0.306

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.81
PhyloP100		0.25

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: rs1009170; hg19: chr14-92636713;