7-77133634-A-G

Variant names:

• chr7-77133634-A-G
• rs12540771
• NM_020879.3:c.-12+10902A>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.-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
• 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]

DTX2P1-UPK3BP1-PMS2P11 (HGNC:42360): (DTX2P1-UPK3BP1-PMS2P11 readthrough, transcribed pseudogene) This locus represents naturally-occurring readthrough transcription spanning multiple pseudogenes: DTX2P1 (DTX2 pseudogene 1), UPK3BP1 (uroplakin 3B pseudogene 1), PMS2P11 (PMS1 homolog 2, mismatch repair system component pseudogene 11). Some transcripts may also extend to PMS2P9 (PMS1 homolog 2, mismatch repair system component pseudogene 9). The readthrough transcripts likely do not encode functional proteins. [provided by RefSeq, Jan 2016]

LOC124901678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.-12+10902A>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.-12+10902A>G		intron	N/A	ENSP00000285871.4
	CCDC146	ENST00000415750.5	TSL:4	c.-12+11166A>G		intron	N/A	ENSP00000388649.1
	DTX2P1-UPK3BP1-PMS2P11	ENST00000579700.2	TSL:2	n.1226-34024A>G		intron	N/A

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

African (AFR) AF: 0.201 AC: 7887 AN: 39266

American (AMR) AF: 0.121 AC: 1753 AN: 14512

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 448 AN: 3420

East Asian (EAS) AF: 0.0194 AC: 97 AN: 4992

South Asian (SAS) AF: 0.0834 AC: 380 AN: 4554

European-Finnish (FIN) AF: 0.352 AC: 3115 AN: 8838

Middle Eastern (MID) AF: 0.0935 AC: 26 AN: 278

European-Non Finnish (NFE) AF: 0.209 AC: 13872 AN: 66448

Other (OTH) AF: 0.163 AC: 327 AN: 2008

Alfa AF: 0.217 Hom.: 435

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.37
PhyloP100		-2.1
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: rs12540771; hg19: chr7-76762951; COSMIC: COSV53549487;