rs5749131

Variant names:

• chr22-30605835-A-G
• rs5749131
• NM_001282327.1:c.-717-318T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282327.1(PES1):​c.-717-318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,122 control chromosomes in the GnomAD database, including 31,111 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 0.62 (31111 hom., cov: 33)
• Consequence: PES1 NM_001282327.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

Genes affected

PES1 (HGNC:8848): (pescadillo ribosomal biogenesis factor 1) This gene encodes a nuclear protein that contains a breast cancer associated gene 1 (BRCA1) C-terminal interaction domain. The encoded protein interacts with BOP1 and WDR12 to form the PeBoW complex, which plays a critical role in cell proliferation via pre-rRNA processing and 60S ribosomal subunit maturation. Expression of this gene may play an important role in breast cancer proliferation and tumorigenicity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the long arm of chromosome 4 and the short arm of chromosome 9. [provided by RefSeq, Aug 2011]

ENSG00000223831 (HGNC:58216):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PES1	NM_001282327.1	c.-717-318T>C		intron_variant	Intron 1 of 16		NP_001269256.1
PES1	NM_001282328.1	c.-764-318T>C		intron_variant	Intron 1 of 16		NP_001269257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PES1	ENST00000402281.5	c.-717-318T>C		intron_variant	Intron 1 of 16	2		ENSP00000384366.1
PES1	ENST00000405677.5	c.-764-318T>C		intron_variant	Intron 1 of 16	2		ENSP00000385654.1
ENSG00000223831	ENST00000432130.1	n.154-757A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94866 AN: 152004 Hom.: 31072 Cov.: 33

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.624 AC: 94959 AN: 152122 Hom.: 31111 Cov.: 33 AF XY: 0.620 AC XY: 46114 AN XY: 74380

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.603

Alfa AF: 0.571 Hom.: 51967

Bravo AF: 0.628

Asia WGS AF: 0.388 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.44
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5749131; hg19: chr22-31001822;