rs10484624

Positions:

• chr6-44437516-G-T

Variant summary

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

The NM_001253.4(CDC5L):​c.2091+7606G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 152,132 control chromosomes in the GnomAD database, including 211 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 0.036 (211 hom., cov: 32)
• Consequence: CDC5L NM_001253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC5L	NM_001253.4	c.2091+7606G>T		intron_variant		ENST00000371477.4	NP_001244.1
POLR1C	NM_001318876.2	c.946-4374G>T		intron_variant			NP_001305805.1
CDC5L	XM_047419605.1	c.1656+7606G>T		intron_variant			XP_047275561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC5L	ENST00000371477.4	c.2091+7606G>T		intron_variant		1	NM_001253.4	ENSP00000360532.3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5497 AN: 152014 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0364 AC: 5534 AN: 152132 Hom.: 211 Cov.: 32 AF XY: 0.0362 AC XY: 2692 AN XY: 74368

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00142

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0173 Hom.: 56

Bravo AF: 0.0404

Asia WGS AF: 0.0390 AC: 134 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10484624; hg19: chr6-44405253;