chr4-185432048-A-C

Variant names:

• chr4-185432048-A-C
• NM_001114357.3:c.167A>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.167A>C​(p.Asp56Ala) 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 1,399,370 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: -0.0150

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]

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=0.028047055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP96	NM_001114357.3	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 8	ENST00000378850.5	NP_001107829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf47	ENST00000378850.5	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 8	1	NM_001114357.3	ENSP00000368127.4
C4orf47	ENST00000511581.5	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 5	3		ENSP00000423127.1
C4orf47	ENST00000511138.5	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 5	3		ENSP00000422279.1
C4orf47	ENST00000508698.3	n.100+2537A>C		intron_variant	Intron 2 of 5	5		ENSP00000425418.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399370 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690192

Gnomad4 AFR exome AF: 0.00

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.46
DANN	Benign	0.88
DEOGEN2	Benign	0.0015	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	.;.;N
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.052
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.089
MutPred		0.24		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.076
ClinPred		0.039	T
GERP RS		-5.0
Varity_R		0.050
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-186353202;