9-37493117-A-G

Position:

• chr9-37493117-A-G

Variant summary

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

The NM_022490.4(POLR1E):​c.402+402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,202 control chromosomes in the GnomAD database, including 42,899 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 0.75 (42899 hom., cov: 33)
• Consequence: POLR1E NM_022490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459

Genes affected

POLR1E (HGNC:17631): (RNA polymerase I subunit E) Predicted to enable DNA binding activity; DNA-directed 5'-3' RNA polymerase activity; and RNA polymerase I general transcription initiation factor binding activity. Involved in nucleolar large rRNA transcription by RNA polymerase I. Located in fibrillar center and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1E	NM_022490.4	c.402+402A>G		intron_variant		ENST00000377798.9	NP_071935.1
POLR1E	NM_001282766.2	c.192+402A>G		intron_variant			NP_001269695.1
POLR1E	XM_047423729.1	c.588+402A>G		intron_variant			XP_047279685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1E	ENST00000377798.9	c.402+402A>G		intron_variant		1	NM_022490.4	ENSP00000367029.4
POLR1E	ENST00000377792.3	c.588+402A>G		intron_variant		2		ENSP00000367023.3
POLR1E	ENST00000442009.6	n.*70+402A>G		intron_variant		2		ENSP00000399887.3

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113283 AN: 152082 Hom.: 42832 Cov.: 33

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.745 AC: 113411 AN: 152202 Hom.: 42899 Cov.: 33 AF XY: 0.754 AC XY: 56083 AN XY: 74404

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.719

Alfa AF: 0.680 Hom.: 46504

Bravo AF: 0.745

Asia WGS AF: 0.896 AC: 3114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs754950; hg19: chr9-37493114;