4-185445507-G-T

Variant names:

• chr4-185445507-G-T
• rs745649959
• NM_152775.4:c.2497C>A

Variant summary

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

The NM_152775.4(CCDC110):​c.2497C>A​(p.His833Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000021 (0 hom.)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

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]

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]

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=0.050514072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.2497C>A	p.His833Asn	missense_variant	Exon 7 of 7	ENST00000307588.8	NP_689988.1
CFAP96	NM_001114357.3	c.881+377G>T		intron_variant	Intron 7 of 7	ENST00000378850.5	NP_001107829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC110	ENST00000307588.8	c.2497C>A	p.His833Asn	missense_variant	Exon 7 of 7	1	NM_152775.4	ENSP00000306776.3
C4orf47	ENST00000378850.5	c.881+377G>T		intron_variant	Intron 7 of 7	1	NM_001114357.3	ENSP00000368127.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1424872 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 710408

Gnomad4 AFR exome AF: 0.0000310

Gnomad4 AMR exome AF: 0.00

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: 9.22e-7

Gnomad4 OTH exome AF: 0.0000169

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	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.0023	.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.41	.;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.36	N;N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.22	B;B
Vest4		0.20
MutPred		0.15		.;Gain of glycosylation at T829 (P = 0.0362);
MVP		0.040
MPC		0.41
ClinPred		0.24	T
GERP RS		-0.73
Varity_R		0.093
gMVP		0.025

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs745649959; hg19: chr4-186366661;