7-77133634-A-G

Position:

• chr7-77133634-A-G

Variant summary

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

The NM_020879.3(CCDC146):​c.-12+10902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 145,204 control chromosomes in the GnomAD database, including 2,922 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 0.19 (2922 hom., cov: 27)
• Consequence: CCDC146 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

Genes affected

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

ENSG00000259628 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC146	NM_020879.3	c.-12+10902A>G		intron_variant		ENST00000285871.5	NP_065930.2
CCDC146	XM_047420662.1	c.-141+10902A>G		intron_variant			XP_047276618.1
CCDC146	XM_047420664.1	c.-10+10902A>G		intron_variant			XP_047276620.1
LOC124901678	XR_007060391.1	n.847-4908T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC146	ENST00000285871.5	c.-12+10902A>G		intron_variant		1	NM_020879.3	ENSP00000285871.4
CCDC146	ENST00000415750.5	c.-12+11166A>G		intron_variant		4		ENSP00000388649.1
ENSG00000259628	ENST00000459742.1	n.59-34024A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 28021 AN: 145172 Hom.: 2920 Cov.: 27

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.0888

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.193 AC: 28045 AN: 145204 Hom.: 2922 Cov.: 27 AF XY: 0.194 AC XY: 13600 AN XY: 70224

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0194

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.163

Alfa AF: 0.217 Hom.: 435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.37

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: rs12540771; hg19: chr7-76762951; COSMIC: COSV53549487;