chr14-99530437-G-A

Variant names:

• chr14-99530437-G-A
• rs4905848
• NM_001144995.2:c.867+5578C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CCNK Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypertelorism and distinctive facies

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85C	NM_001144995.2	MANE Select	c.867+5578C>T		intron	N/A	NP_001138467.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC85C	ENST00000380243.9	TSL:5 MANE Select	c.867+5578C>T		intron	N/A	ENSP00000369592.4
	CCNK	ENST00000555049.5	TSL:1	c.1118-4227G>A		intron	N/A	ENSP00000452307.1
	CCDC85C	ENST00000554996.5	TSL:4	c.180+5578C>T		intron	N/A	ENSP00000451294.1

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

African (AFR) AF: 0.352 AC: 14600 AN: 41492

American (AMR) AF: 0.587 AC: 8973 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1721 AN: 3462

East Asian (EAS) AF: 0.537 AC: 2758 AN: 5140

South Asian (SAS) AF: 0.594 AC: 2856 AN: 4808

European-Finnish (FIN) AF: 0.430 AC: 4540 AN: 10558

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33906 AN: 67958

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.471 Hom.: 2226

Bravo AF: 0.474

Asia WGS AF: 0.522 AC: 1817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.72
DANN	Benign	0.75
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4905848; hg19: chr14-99996774;