rs113175413

Variant names:

• chr8-17246633-C-G
• rs113175413
• NM_013354.7:c.-96+42G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-17246633-C-G
• chr8-17246633-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013354.7(CNOT7):​c.-96+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 157,830 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (0 hom.)
• Consequence: CNOT7 NM_013354.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-17246633-C-G is Benign according to our data. Variant chr8-17246633-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1219001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0122 (1860/152326) while in subpopulation NFE AF = 0.0213 (1451/68024). AF 95% confidence interval is 0.0204. There are 19 homozygotes in GnomAd4. There are 832 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1860 AD gene.

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.-96+42G>C		intron	N/A	NP_037486.2	Q9UIV1-1
	CNOT7	NM_001322093.2		c.-96+42G>C		intron	N/A	NP_001309022.1
	CNOT7	NM_001322090.2		c.-171+42G>C		intron	N/A	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.-96+42G>C		intron	N/A	ENSP00000355279.4	Q9UIV1-1
	CNOT7	ENST00000851024.1		c.-96+42G>C		intron	N/A	ENSP00000521093.1
	CNOT7	ENST00000851025.1		c.-96+851G>C		intron	N/A	ENSP00000521094.1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1862 AN: 152208 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00441

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00545 AC: 30 AN: 5504 Hom.: 0 Cov.: 0 AF XY: 0.00558 AC XY: 18 AN XY: 3228

African (AFR) AF: 0.00 AC: 0 AN: 24

American (AMR) AF: 0.00 AC: 0 AN: 72

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 56

East Asian (EAS) AF: 0.00 AC: 0 AN: 46

South Asian (SAS) AF: 0.00199 AC: 4 AN: 2008

European-Finnish (FIN) AF: 0.00410 AC: 1 AN: 244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 20

European-Non Finnish (NFE) AF: 0.00848 AC: 24 AN: 2830

Other (OTH) AF: 0.00490 AC: 1 AN: 204

GnomAD4 genome AF: 0.0122 AC: 1860 AN: 152326 Hom.: 19 Cov.: 32 AF XY: 0.0112 AC XY: 832 AN XY: 74488

African (AFR) AF: 0.00440 AC: 183 AN: 41584

American (AMR) AF: 0.00536 AC: 82 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4828

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1451 AN: 68024

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.0142 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.84
PhyloP100		-0.085
PromoterAI		0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113175413; hg19: chr8-17104142;