dbSNP rs4905848: CCDC85C:c.867+5578C>T (chr14-99530437-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.94

Publications

1 publications found

Variant links:

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]

CCDC85C links:

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

CCNK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCDC85C	NM_001144995.2 link	c.867+5578C>T	intron_variant	Intron 2 of 5	ENST00000380243.9	NP_001138467.1	A6NKD9
CCDC85C	XM_011536706.3 link	c.868-2181C>T	intron_variant	Intron 2 of 3		XP_011535008.1
CCDC85C	XM_047431328.1 link	c.868-4157C>T	intron_variant	Intron 2 of 2		XP_047287284.1
CCDC85C	XM_011536707.3 link	c.868-2181C>T	intron_variant	Intron 2 of 3		XP_011535009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC85C	ENST00000380243.9 link	c.867+5578C>T		intron_variant	Intron 2 of 5	5	NM_001144995.2	ENSP00000369592.4		A6NKD9

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70774

AN:

151898

Hom.:

16922

Cov.:

show subpopulations

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.:

AF XY:

0.467

AC XY:

34720

AN XY:

74290

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1945

3891

5836

7782

9727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.72

(source)

DANN

Benign

0.75

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over