8-17245065-C-T

Variant names:

• chr8-17245065-C-T
• rs1810721768
• NM_013354.7:c.88G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013354.7(CNOT7):​c.88G>A​(p.Val30Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNOT7 NM_013354.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10153952).

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.88G>A	p.Val30Ile	missense	Exon 2 of 7	NP_037486.2	Q9UIV1-1
	CNOT7	NM_001322093.2		c.88G>A	p.Val30Ile	missense	Exon 2 of 8	NP_001309022.1
	CNOT7	NM_001322090.2		c.88G>A	p.Val30Ile	missense	Exon 3 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.88G>A	p.Val30Ile	missense	Exon 2 of 7	ENSP00000355279.4	Q9UIV1-1
	CNOT7	ENST00000851024.1		c.88G>A	p.Val30Ile	missense	Exon 2 of 8	ENSP00000521093.1
	CNOT7	ENST00000851025.1		c.88G>A	p.Val30Ile	missense	Exon 2 of 7	ENSP00000521094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461410 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727020

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111764

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N
PhyloP100		3.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.54		Loss of MoRF binding (P = 0.1086)
MVP		0.15
MPC		0.67
ClinPred		0.47	T
GERP RS		3.8
PromoterAI		-0.023	Neutral
Varity_R		0.15
gMVP		0.40
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1810721768; hg19: chr8-17102574;