chr7-77239090-A-G

Variant names:

• chr7-77239090-A-G
• rs10499830
• NM_020879.3:c.239+2061A>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.239+2061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,242 control chromosomes in the GnomAD database, including 488 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 0.051 (488 hom., cov: 32)
• Consequence: CCDC146 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• 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

ENSG00000299512 (HGNC:):

CCDC146-AS1 (HGNC:58425):

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 (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC146	NM_020879.3	c.239+2061A>G		intron_variant	Intron 3 of 18	ENST00000285871.5	NP_065930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC146	ENST00000285871.5	c.239+2061A>G		intron_variant	Intron 3 of 18	1	NM_020879.3	ENSP00000285871.4
CCDC146	ENST00000415750.5	c.239+2061A>G		intron_variant	Intron 3 of 4	4		ENSP00000388649.1
ENSG00000299512	ENST00000764184.1	n.189+6236T>C		intron_variant	Intron 1 of 2
ENSG00000299512	ENST00000764185.1	n.153+6236T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7749 AN: 152124 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0641

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00573

Gnomad OTH AF: 0.0382

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

GnomAD4 genome AF: 0.0510 AC: 7764 AN: 152242 Hom.: 488 Cov.: 32 AF XY: 0.0499 AC XY: 3713 AN XY: 74436

African (AFR) AF: 0.152 AC: 6317 AN: 41508

American (AMR) AF: 0.0236 AC: 361 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3470

East Asian (EAS) AF: 0.0643 AC: 333 AN: 5180

South Asian (SAS) AF: 0.0385 AC: 186 AN: 4826

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10624

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00573 AC: 390 AN: 68018

Other (OTH) AF: 0.0378 AC: 80 AN: 2116

Alfa AF: 0.0238 Hom.: 248

Bravo AF: 0.0585

Asia WGS AF: 0.0410 AC: 143 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	3.4
DANN	Benign	0.48
PhyloP100		-0.085
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: rs10499830; hg19: chr7-76868407;