7-77136737-A-G

Variant names:

• chr7-77136737-A-G
• rs2539149
• NM_020879.3:c.-12+14005A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020879.3(CCDC146):​c.-12+14005A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00025 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CCDC146 NM_020879.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• 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]

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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+14005A>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+14005A>G		intron	N/A	ENSP00000285871.4
	CCDC146	ENST00000415750.5	TSL:4	c.-12+14269A>G		intron	N/A	ENSP00000388649.1
	DTX2P1-UPK3BP1-PMS2P11	ENST00000579700.2	TSL:2	n.1226-30921A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000242 AC: 33 AN: 136514 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000617

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.000688

Gnomad FIN AF: 0.000107

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.0000484

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000249 AC: 34 AN: 136596 Hom.: 0 Cov.: 31 AF XY: 0.000211 AC XY: 14 AN XY: 66360

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000460 AC: 17 AN: 36956

American (AMR) AF: 0.000616 AC: 8 AN: 12986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3156

East Asian (EAS) AF: 0.000204 AC: 1 AN: 4914

South Asian (SAS) AF: 0.000689 AC: 3 AN: 4354

European-Finnish (FIN) AF: 0.000107 AC: 1 AN: 9322

Middle Eastern (MID) AF: 0.00403 AC: 1 AN: 248

European-Non Finnish (NFE) AF: 0.0000484 AC: 3 AN: 61934

Other (OTH) AF: 0.00 AC: 0 AN: 1864

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00637 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		0.22

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: rs2539149; hg19: chr7-76766054;