1-16924341-A-G

Position:

• chr1-16924341-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_014675.5(CROCC):​c.213A>G​(p.Thr71Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (12 hom., cov: 50)
  • Exomes 𝑓: 0.32 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: CROCC NM_014675.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.482

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-16924341-A-G is Benign according to our data. Variant chr1-16924341-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 767658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.482 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CROCC	NM_014675.5	c.213A>G	p.Thr71Thr	synonymous_variant	3/37	ENST00000375541.10	NP_055490.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CROCC	ENST00000375541.10	c.213A>G	p.Thr71Thr	synonymous_variant	3/37	5	NM_014675.5	ENSP00000364691.4
CROCC	ENST00000445545.6	c.60A>G	p.Thr20Thr	synonymous_variant	2/24	5		ENSP00000402626.2
CROCC	ENST00000467938.5	c.30+1543A>G		intron_variant		2		ENSP00000480016.1
CROCC	ENST00000466256.6	n.126-5945A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 51325 AN: 149588 Hom.: 12 Cov.: 50 FAILED QC

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.366

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.324 AC: 466158 AN: 1439958 Hom.: 14 Cov.: 72 AF XY: 0.322 AC XY: 230449 AN XY: 716204

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.343 AC: 51367 AN: 149696 Hom.: 12 Cov.: 50 AF XY: 0.343 AC XY: 25055 AN XY: 73130

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.363

Alfa AF: 0.336 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.85
DANN	Benign	0.38

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: rs57174186; hg19: chr1-17250836; COSMIC: COSV65011423;