rs3114316

Variant names:

• chr7-77253605-C-T
• rs3114316
• NM_020879.3:c.450-901C>T

Variant summary

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

The NM_020879.3(CCDC146):​c.450-901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,116 control chromosomes in the GnomAD database, including 43,052 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 0.74 (43052 hom., cov: 33)
• Consequence: CCDC146 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 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

ENSG00000250990 (HGNC:58425):

LOC102723791 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC146	NM_020879.3	c.450-901C>T		intron_variant	Intron 4 of 18	ENST00000285871.5	NP_065930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC146	ENST00000285871.5	c.450-901C>T		intron_variant	Intron 4 of 18	1	NM_020879.3	ENSP00000285871.4
CCDC146	ENST00000415750.5	c.450-901C>T		intron_variant	Intron 4 of 4	4		ENSP00000388649.1
CCDC146	ENST00000461882.1	n.86-901C>T		intron_variant	Intron 1 of 3	3
ENSG00000250990	ENST00000476561.2	n.422+1721G>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112082 AN: 151998 Hom.: 43038 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.737 AC: 112145 AN: 152116 Hom.: 43052 Cov.: 33 AF XY: 0.732 AC XY: 54396 AN XY: 74356

African (AFR) AF: 0.530 AC: 21975 AN: 41456

American (AMR) AF: 0.698 AC: 10667 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2920 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2872 AN: 5172

South Asian (SAS) AF: 0.821 AC: 3962 AN: 4824

European-Finnish (FIN) AF: 0.768 AC: 8116 AN: 10572

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58913 AN: 68018

Other (OTH) AF: 0.759 AC: 1607 AN: 2116

Alfa AF: 0.703 Hom.: 10840

Bravo AF: 0.722

Asia WGS AF: 0.696 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.49
PhyloP100		-0.031
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: rs3114316; hg19: chr7-76882922;