rs4445835

Positions:

• chr14-99557059-C-A
• chr14-99557059-C-G
• chr14-99557059-C-T

Variant summary

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

The NM_001144995.2(CCDC85C):​c.794-20971G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,076 control chromosomes in the GnomAD database, including 22,268 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 0.54 (22268 hom., cov: 33)
• Consequence: CCDC85C NM_001144995.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC85C	NM_001144995.2	c.794-20971G>T		intron_variant		ENST00000380243.9	NP_001138467.1
CCDC85C	XM_011536706.3	c.794-20971G>T		intron_variant			XP_011535008.1
CCDC85C	XM_011536707.3	c.794-20971G>T		intron_variant			XP_011535009.1
CCDC85C	XM_047431328.1	c.794-20971G>T		intron_variant			XP_047287284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC85C	ENST00000380243.9	c.794-20971G>T		intron_variant		5	NM_001144995.2	ENSP00000369592	P1
CCDC85C	ENST00000554877.1	c.-273+19404G>T		intron_variant		4		ENSP00000452300
CCDC85C	ENST00000554996.5	c.107-20971G>T		intron_variant		4		ENSP00000451294
CCDC85C	ENST00000556348.1	c.49+15661G>T		intron_variant		5		ENSP00000451718

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81735 AN: 151956 Hom.: 22234 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.538 AC: 81825 AN: 152076 Hom.: 22268 Cov.: 33 AF XY: 0.533 AC XY: 39662 AN XY: 74346

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.526

Alfa AF: 0.473 Hom.: 3635

Bravo AF: 0.554

Asia WGS AF: 0.547 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.85

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: rs4445835; hg19: chr14-100023396;