6-43516985-C-CGGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000646188.1(POLR1C):c.-96-318_-96-316dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,251,552 control chromosomes in the GnomAD database, including 306 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (25 hom., cov: 32)
  • Exomes 𝑓: 0.019 (281 hom.)
• Consequence: POLR1C ENST00000646188.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38

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]

YIPF3 (HGNC:21023): (Yip1 domain family member 3) Predicted to be involved in cell differentiation. Located in Golgi apparatus and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-43516985-C-CGGG is Benign according to our data. Variant chr6-43516985-C-CGGG is described in ClinVar as [Likely_benign]. Clinvar id is 2580819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.015 (2264/151386) while in subpopulation SAS AF= 0.0332 (160/4824). AF 95% confidence interval is 0.029. There are 25 homozygotes in gnomad4. There are 1053 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1C	ENST00000428025.6	c.-96-318_-96-316dup		intron_variant		4
POLR1C	ENST00000646188.1	c.-96-318_-96-316dup		intron_variant
YIPF3	ENST00000503972.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2263 AN: 151272 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00421

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.0186 AC: 20464 AN: 1100166 Hom.: 281 Cov.: 15 AF XY: 0.0192 AC XY: 10778 AN XY: 562100

Gnomad4 AFR exome AF: 0.00367

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00783

Gnomad4 EAS exome AF: 0.000528

Gnomad4 SAS exome AF: 0.0288

Gnomad4 FIN exome AF: 0.00374

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0181

GnomAD4 genome AF: 0.0150 AC: 2264 AN: 151386 Hom.: 25 Cov.: 32 AF XY: 0.0142 AC XY: 1053 AN XY: 74052

Gnomad4 AFR AF: 0.00418

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201485043; hg19: chr6-43484723;