chr11-83165228-T-G

Variant names:

• chr11-83165228-T-G
• rs1943345
• NM_001346413.3:c.703-372T>G

Variant summary

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

The NM_001346413.3(PCF11):​c.703-372T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,174 control chromosomes in the GnomAD database, including 4,876 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 0.24 (4876 hom., cov: 32)
• Consequence: PCF11 NM_001346413.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 8 publications found

Genes affected

PCF11 (HGNC:30097): (PCF11 cleavage and polyadenylation factor subunit) The protein encoded by this gene binds to CLP1 to form pre-mRNA cleavage factor IIm. The encoded protein is necessary for efficient Pol II transcription termination and may be involved in degradation of the 3' product of polyA site cleavage. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCF11	NM_001346413.3	c.703-372T>G		intron_variant	Intron 4 of 15	ENST00000690938.1	NP_001333342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCF11	ENST00000690938.1	c.703-372T>G		intron_variant	Intron 4 of 15		NM_001346413.3	ENSP00000508500.1
PCF11	ENST00000298281.8	c.703-372T>G		intron_variant	Intron 4 of 15	1		ENSP00000298281.4
PCF11	ENST00000530304.5	c.703-372T>G		intron_variant	Intron 4 of 7	1		ENSP00000431567.1
PCF11	ENST00000530660.5	c.703-372T>G		intron_variant	Intron 4 of 7	2		ENSP00000434540.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35817 AN: 152056 Hom.: 4874 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35824 AN: 152174 Hom.: 4876 Cov.: 32 AF XY: 0.242 AC XY: 18015 AN XY: 74398

African (AFR) AF: 0.120 AC: 4980 AN: 41536

American (AMR) AF: 0.257 AC: 3930 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3468

East Asian (EAS) AF: 0.527 AC: 2732 AN: 5182

South Asian (SAS) AF: 0.383 AC: 1850 AN: 4832

European-Finnish (FIN) AF: 0.272 AC: 2877 AN: 10570

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17611 AN: 67984

Other (OTH) AF: 0.261 AC: 550 AN: 2110

Alfa AF: 0.250 Hom.: 8812

Bravo AF: 0.229

Asia WGS AF: 0.417 AC: 1450 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.83
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs1943345; hg19: chr11-82876270;