rs6696928

chr1-16963563-A-Gchr1-16963563-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014675.5(CROCC):c.4406-2160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,180 control chromosomes in the GnomAD database, including 60,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60950 hom., cov: 31)
• Consequence: CROCC NM_014675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CROCC	NM_014675.5	c.4406-2160A>G		intron_variant		ENST00000375541.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CROCC	ENST00000375541.10	c.4406-2160A>G		intron_variant		5	NM_014675.5	P1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136022 AN: 152062 Hom.: 60896 Cov.: 31

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.897

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.895 AC: 136134 AN: 152180 Hom.: 60950 Cov.: 31 AF XY: 0.895 AC XY: 66591 AN XY: 74366

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.933

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.897

Alfa AF: 0.894 Hom.: 12820

Bravo AF: 0.897

Asia WGS AF: 0.919 AC: 3195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.28
Dann	Benign	0.76

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: rs6696928; hg19: chr1-17290058;