rs4905848

Positions:

• chr14-99530437-G-A

Variant summary

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

The NM_001144995.2(CCDC85C):​c.867+5578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,016 control chromosomes in the GnomAD database, including 16,928 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 0.47 (16928 hom., cov: 32)
• Consequence: CCDC85C NM_001144995.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94

Genes affected

CCDC85C (HGNC:35459): (coiled-coil domain containing 85C) Predicted to be involved in cerebral cortex development. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CCNK (HGNC:1596): (cyclin K) The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC85C	NM_001144995.2	c.867+5578C>T		intron_variant		ENST00000380243.9	NP_001138467.1
CCDC85C	XM_011536706.3	c.868-2181C>T		intron_variant			XP_011535008.1
CCDC85C	XM_047431328.1	c.868-4157C>T		intron_variant			XP_047287284.1
CCDC85C	XM_011536707.3	c.868-2181C>T		intron_variant			XP_011535009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC85C	ENST00000380243.9	c.867+5578C>T		intron_variant		5	NM_001144995.2	ENSP00000369592.4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70774 AN: 151898 Hom.: 16922 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.466 AC: 70800 AN: 152016 Hom.: 16928 Cov.: 32 AF XY: 0.467 AC XY: 34720 AN XY: 74290

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.485

Alfa AF: 0.475 Hom.: 2177

Bravo AF: 0.474

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.75

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: rs4905848; hg19: chr14-99996774;