chr4-185445102-G-C

Variant names:

• chr4-185445102-G-C
• rs201058690
• NM_001114357.3:c.853G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001114357.3(CFAP96):​c.853G>C​(p.Glu285Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CFAP96 NM_001114357.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

Genes affected

CFAP96 (HGNC:34346): (cilia and flagella associated protein 96) Located in 9+0 non-motile cilium; centrosome; and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CCDC110 (HGNC:28504): (coiled-coil domain containing 110) Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048009694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP96	NM_001114357.3	c.853G>C	p.Glu285Gln	missense_variant	Exon 7 of 8	ENST00000378850.5	NP_001107829.1
CCDC110	NM_152775.4	c.*400C>G		downstream_gene_variant		ENST00000307588.8	NP_689988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf47	ENST00000378850.5	c.853G>C	p.Glu285Gln	missense_variant	Exon 7 of 8	1	NM_001114357.3	ENSP00000368127.4
CCDC110	ENST00000307588.8	c.*400C>G		downstream_gene_variant		1	NM_152775.4	ENSP00000306776.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399302 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.00058	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PROVEAN	Benign	0.090	N
REVEL	Benign	0.097
Sift	Benign	0.46	T
Sift4G	Benign	0.55	T
Polyphen		0.56	P
Vest4		0.065
MutPred		0.13		Gain of MoRF binding (P = 0.0356);
MVP		0.048
ClinPred		0.085	T
GERP RS		1.1
Varity_R		0.041
gMVP		0.24

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: rs201058690; hg19: chr4-186366256;