rs3091260

Variant names:

• chr7-77201078-T-A
• rs3091260
• NM_020879.3:c.156+33254T>A

Variant summary

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

The NM_020879.3(CCDC146):​c.156+33254T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,034 control chromosomes in the GnomAD database, including 17,590 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 0.45 (17590 hom., cov: 32)
• Consequence: CCDC146 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC146	NM_020879.3	c.156+33254T>A		intron_variant	Intron 2 of 18	ENST00000285871.5	NP_065930.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC146	ENST00000285871.5	c.156+33254T>A		intron_variant	Intron 2 of 18	1	NM_020879.3	ENSP00000285871.4
CCDC146	ENST00000415750.5	c.156+33254T>A		intron_variant	Intron 2 of 4	4		ENSP00000388649.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67622 AN: 151916 Hom.: 17553 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.445 AC: 67708 AN: 152034 Hom.: 17590 Cov.: 32 AF XY: 0.447 AC XY: 33199 AN XY: 74332

African (AFR) AF: 0.721 AC: 29891 AN: 41444

American (AMR) AF: 0.429 AC: 6547 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2821 AN: 5164

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4824

European-Finnish (FIN) AF: 0.355 AC: 3753 AN: 10580

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20942 AN: 67964

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.375 Hom.: 1695

Bravo AF: 0.463

Asia WGS AF: 0.432 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.085
DANN	Benign	0.46
PhyloP100		-0.90
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: rs3091260; hg19: chr7-76830395;