chr8-17237307-A-G

Variant names:

• chr8-17237307-A-G
• rs915272393
• NM_013354.7:c.378T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_013354.7(CNOT7):​c.378T>C​(p.His126His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNOT7 NM_013354.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 0 publications found

Genes affected

CNOT7 (HGNC:14101): (CCR4-NOT transcription complex subunit 7) The protein encoded by this gene binds to an anti-proliferative protein, B-cell translocation protein 1, which negatively regulates cell proliferation. Binding of the two proteins, which is driven by phosphorylation of the anti-proliferative protein, causes signaling events in cell division that lead to changes in cell proliferation associated with cell-cell contact. The encoded protein downregulates the innate immune response and therefore provides a therapeutic target for enhancing its antimicrobial activity against foreign agents. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP7: Synonymous conserved (PhyloP=0.631 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013354.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT7	NM_013354.7	MANE Select	c.378T>C	p.His126His	synonymous	Exon 4 of 7	NP_037486.2	Q9UIV1-1
	CNOT7	NM_001322093.2		c.444T>C	p.His148His	synonymous	Exon 5 of 8	NP_001309022.1
	CNOT7	NM_001322090.2		c.378T>C	p.His126His	synonymous	Exon 5 of 8	NP_001309019.1	Q9UIV1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT7	ENST00000361272.9	TSL:1 MANE Select	c.378T>C	p.His126His	synonymous	Exon 4 of 7	ENSP00000355279.4	Q9UIV1-1
	CNOT7	ENST00000851024.1		c.444T>C	p.His148His	synonymous	Exon 5 of 8	ENSP00000521093.1
	CNOT7	ENST00000851025.1		c.378T>C	p.His126His	synonymous	Exon 4 of 7	ENSP00000521094.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461776 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111918

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.63

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: rs915272393; hg19: chr8-17094816;