rs10488500

Positions:

• chr7-77211942-A-G

Variant summary

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

The ENST00000285871.5(CCDC146):​c.157-25005A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,198 control chromosomes in the GnomAD database, including 499 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 0.065 (499 hom., cov: 31)
• Consequence: CCDC146 ENST00000285871.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

Genes affected

CCDC146 (HGNC:29296): (coiled-coil domain containing 146) Located in centriole. [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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC146	NM_020879.3	c.157-25005A>G		intron_variant		ENST00000285871.5	NP_065930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC146	ENST00000285871.5	c.157-25005A>G		intron_variant		1	NM_020879.3	ENSP00000285871	P1
CCDC146	ENST00000415750.5	c.157-25005A>G		intron_variant		4		ENSP00000388649

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9881 AN: 152080 Hom.: 499 Cov.: 31

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0649 AC: 9883 AN: 152198 Hom.: 499 Cov.: 31 AF XY: 0.0659 AC XY: 4905 AN XY: 74406

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0245

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0912

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0837 Hom.: 368

Bravo AF: 0.0542

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.72

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: rs10488500; hg19: chr7-76841259;