1-16922784-A-G

Position:

• chr1-16922784-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014675.5(CROCC):​c.182A>G​(p.Gln61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 45)
• Consequence: CROCC NM_014675.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.546

Genes affected

CROCC (HGNC:21299): (ciliary rootlet coiled-coil, rootletin) Predicted to enable kinesin binding activity and structural molecule activity. Involved in several processes, including centriole-centriole cohesion; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CROCC (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0562571).
• BP6: Variant 1-16922784-A-G is Benign according to our data. Variant chr1-16922784-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2516241.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CROCC	NM_014675.5	c.182A>G	p.Gln61Arg	missense_variant	2/37	ENST00000375541.10	NP_055490.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CROCC	ENST00000375541.10	c.182A>G	p.Gln61Arg	missense_variant	2/37	5	NM_014675.5	ENSP00000364691.4
CROCC	ENST00000445545.6	c.29A>G	p.Gln10Arg	missense_variant	1/24	5		ENSP00000402626.2
CROCC	ENST00000467938.5	c.16A>G	p.Ser6Gly	missense_variant	1/17	2		ENSP00000480016.1
CROCC	ENST00000466256.6	n.126-7502A>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 45

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 45

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.43
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.031
Sift	Benign	0.61	T
Sift4G	Benign	0.36	T
Vest4		0.23
MutPred		0.21		Loss of loop (P = 9e-04);
MVP		0.081
MPC		0.044
ClinPred		0.092	T
GERP RS		-0.045
gMVP		0.060

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: chr1-17249279;