rs10488500

Variant names:

• chr7-77211942-A-G
• rs10488500
• NM_020879.3:c.157-25005A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020879.3(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 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 3 publications found

Genes affected

CCDC146 (HGNC:29296): (coiled-coil domain containing 146) Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

CCDC146 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020879.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC146	NM_020879.3	MANE Select	c.157-25005A>G		intron	N/A	NP_065930.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC146	ENST00000285871.5	TSL:1 MANE Select	c.157-25005A>G		intron	N/A	ENSP00000285871.4
	CCDC146	ENST00000415750.5	TSL:4	c.157-25005A>G		intron	N/A	ENSP00000388649.1

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

African (AFR) AF: 0.0134 AC: 557 AN: 41552

American (AMR) AF: 0.0729 AC: 1114 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1487 AN: 10578

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0912 AC: 6202 AN: 67996

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0833 Hom.: 397

Bravo AF: 0.0542

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.2
DANN	Benign	0.72
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10488500; hg19: chr7-76841259;