9-121090387-C-T

Variant names:

• chr9-121090387-C-T
• rs117390062
• NM_007018.6:c.330C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001369895.1(CNTRL):​c.-41C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,609,856 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (35 hom.)
• Consequence: CNTRL NM_001369895.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-121090387-C-T is Benign according to our data. Variant chr9-121090387-C-T is described in ClinVar as Benign. ClinVar VariationId is 719184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369895.1. 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.330C>T	p.Asp110Asp	synonymous	Exon 4 of 44	NP_008949.4
	CNTRL	NM_001369895.1		c.-41C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 32	NP_001356824.1
	CNTRL	NM_001369893.1		c.330C>T	p.Asp110Asp	synonymous	Exon 3 of 32	NP_001356822.1	Q5JVD1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTRL	ENST00000373855.7	TSL:5 MANE Select	c.330C>T	p.Asp110Asp	synonymous	Exon 4 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.330C>T	p.Asp110Asp	synonymous	Exon 3 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000693191.1		c.-41C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000509059.1	A0A8I5KPU9

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152094 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00588

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00476 AC: 1177 AN: 247354 AF XY: 0.00444

Gnomad AFR exome AF: 0.000931

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.000401

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.0166

Gnomad NFE exome AF: 0.00662

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00568 AC: 8281 AN: 1457644 Hom.: 35 Cov.: 30 AF XY: 0.00551 AC XY: 3995 AN XY: 725104

African (AFR) AF: 0.000750 AC: 25 AN: 33314

American (AMR) AF: 0.00100 AC: 44 AN: 44002

Ashkenazi Jewish (ASJ) AF: 0.000269 AC: 7 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.000117 AC: 10 AN: 85350

European-Finnish (FIN) AF: 0.0174 AC: 922 AN: 53058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00635 AC: 7057 AN: 1110484

Other (OTH) AF: 0.00359 AC: 216 AN: 60214

GnomAD4 genome AF: 0.00440 AC: 669 AN: 152212 Hom.: 5 Cov.: 32 AF XY: 0.00477 AC XY: 355 AN XY: 74426

African (AFR) AF: 0.000987 AC: 41 AN: 41520

American (AMR) AF: 0.000654 AC: 10 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0203 AC: 214 AN: 10566

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

European-Non Finnish (NFE) AF: 0.00588 AC: 400 AN: 68024

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00464 Hom.: 2

Bravo AF: 0.00287

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.8
DANN	Benign	0.52
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs117390062; hg19: chr9-123852665;