NM_007018.6:c.4075C>T

Variant names:

• chr9-121152596-C-T
• rs9408926
• NM_007018.6:c.4075C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007018.6(CNTRL):​c.4075C>T​(p.Leu1359Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,613,616 control chromosomes in the GnomAD database, including 2,267 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 0.039 (130 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2137 hom.)
• Consequence: CNTRL NM_007018.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• Publications: 17 publications found

Genes affected

CNTRL (HGNC:1858): (centriolin) This gene encodes a centrosomal protein required for the centrosome to function as a microtubule organizing center. The gene product is also associated with centrosome maturation. One version of stem cell myeloproliferative disorder is the result of a reciprocal translocation between chromosomes 8 and 9, with the breakpoint associated with fibroblast growth factor receptor 1 and centrosomal protein 1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-0.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007018.6. 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
	CNTRL	NM_007018.6	MANE Select	c.4075C>T	p.Leu1359Leu	synonymous	Exon 26 of 44	NP_008949.4
	CNTRL	NM_001330762.2		c.2419C>T	p.Leu807Leu	synonymous	Exon 15 of 33	NP_001317691.1	Q7Z7A1-2
	CNTRL	NM_001369892.1		c.2419C>T	p.Leu807Leu	synonymous	Exon 15 of 32	NP_001356821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.4075C>T	p.Leu1359Leu	synonymous	Exon 26 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.4075C>T	p.Leu1359Leu	synonymous	Exon 25 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000373845.6	TSL:1	n.554C>T		non_coding_transcript_exon	Exon 1 of 19

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5885 AN: 152124 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0364

GnomAD2 exomes AF: 0.0378 AC: 9492 AN: 251192 AF XY: 0.0378

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.0189

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.00147

Gnomad FIN exome AF: 0.0550

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0421

GnomAD4 exome AF: 0.0506 AC: 73939 AN: 1461374 Hom.: 2137 Cov.: 31 AF XY: 0.0495 AC XY: 36014 AN XY: 727022

African (AFR) AF: 0.0219 AC: 734 AN: 33472

American (AMR) AF: 0.0202 AC: 903 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 642 AN: 26130

East Asian (EAS) AF: 0.00504 AC: 200 AN: 39684

South Asian (SAS) AF: 0.0173 AC: 1492 AN: 86250

European-Finnish (FIN) AF: 0.0557 AC: 2975 AN: 53416

Middle Eastern (MID) AF: 0.0309 AC: 178 AN: 5768

European-Non Finnish (NFE) AF: 0.0576 AC: 64013 AN: 1111558

Other (OTH) AF: 0.0464 AC: 2802 AN: 60372

GnomAD4 genome AF: 0.0387 AC: 5887 AN: 152242 Hom.: 130 Cov.: 32 AF XY: 0.0365 AC XY: 2718 AN XY: 74422

African (AFR) AF: 0.0230 AC: 955 AN: 41546

American (AMR) AF: 0.0250 AC: 383 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5184

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4820

European-Finnish (FIN) AF: 0.0501 AC: 531 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3734 AN: 68018

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0485 Hom.: 966

Bravo AF: 0.0374

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.0531

EpiControl AF: 0.0507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		-0.81
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: rs9408926; hg19: chr9-123914874;