rs3734693

Positions:

• chr6-43997428-T-C

Variant summary

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

The NM_001318876.2(POLR1C):​c.946-444462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,092 control chromosomes in the GnomAD database, including 13,667 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 0.35 (13666 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: POLR1C NM_001318876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

POLR1C (HGNC:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SCIRT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1C	NM_001318876.2	c.946-444462T>C		intron_variant			NP_001305805.1
SCIRT	NR_125864.1	n.647-120A>G		intron_variant
SCIRT	NR_125865.1	n.431-120A>G		intron_variant
LOC124901321	XR_007059591.1	n.43-1523T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCIRT	ENST00000422059.5	n.647-120A>G		intron_variant		2
SCIRT	ENST00000607590.1	n.430-120A>G		intron_variant		3
SCIRT	ENST00000652850.1	n.450-120A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52534 AN: 151902 Hom.: 13612 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.153 AC: 11 AN: 72 Hom.: 1 AF XY: 0.196 AC XY: 11 AN XY: 56

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.346 AC: 52657 AN: 152020 Hom.: 13666 Cov.: 32 AF XY: 0.346 AC XY: 25698 AN XY: 74300

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.324

Alfa AF: 0.194 Hom.: 7554

Bravo AF: 0.373

Asia WGS AF: 0.416 AC: 1449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3734693; hg19: chr6-43965165;