rs3736855

Variant names:

• chr9-121154742-T-A
• rs3736855
• NM_007018.6:c.4194T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-121154742-T-A
• chr9-121154742-T-G

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.4194T>A​(p.Val1398Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,597,718 control chromosomes in the GnomAD database, including 161,749 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 0.38 (12670 hom., cov: 32)
  • Exomes 𝑓: 0.45 (149079 hom.)
• Consequence: CNTRL NM_007018.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 19 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=-0.53).
• BP7: Synonymous conserved (PhyloP=0.086 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 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.4194T>A	p.Val1398Val	synonymous	Exon 27 of 44	NP_008949.4
	CNTRL	NM_001330762.2		c.2538T>A	p.Val846Val	synonymous	Exon 16 of 33	NP_001317691.1	Q7Z7A1-2
	CNTRL	NM_001369892.1		c.2538T>A	p.Val846Val	synonymous	Exon 16 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.4194T>A	p.Val1398Val	synonymous	Exon 27 of 44	ENSP00000362962.1	Q7Z7A1-1
	CNTRL	ENST00000373847.6	TSL:1	c.4194T>A	p.Val1398Val	synonymous	Exon 26 of 32	ENSP00000362953.2	Q5JVD1
	CNTRL	ENST00000373845.6	TSL:1	n.673T>A		non_coding_transcript_exon	Exon 2 of 19

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58319 AN: 151952 Hom.: 12658 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.472 AC: 118174 AN: 250396 AF XY: 0.484

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.447 AC: 645759 AN: 1445648 Hom.: 149079 Cov.: 30 AF XY: 0.454 AC XY: 326839 AN XY: 720184

African (AFR) AF: 0.164 AC: 5460 AN: 33294

American (AMR) AF: 0.540 AC: 24099 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 13136 AN: 25986

East Asian (EAS) AF: 0.529 AC: 20909 AN: 39546

South Asian (SAS) AF: 0.651 AC: 55811 AN: 85732

European-Finnish (FIN) AF: 0.462 AC: 24630 AN: 53326

Middle Eastern (MID) AF: 0.508 AC: 2763 AN: 5442

European-Non Finnish (NFE) AF: 0.430 AC: 472309 AN: 1097812

Other (OTH) AF: 0.445 AC: 26642 AN: 59852

GnomAD4 genome AF: 0.384 AC: 58349 AN: 152070 Hom.: 12670 Cov.: 32 AF XY: 0.394 AC XY: 29270 AN XY: 74336

African (AFR) AF: 0.175 AC: 7241 AN: 41494

American (AMR) AF: 0.494 AC: 7547 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2863 AN: 5170

South Asian (SAS) AF: 0.645 AC: 3112 AN: 4826

European-Finnish (FIN) AF: 0.487 AC: 5145 AN: 10564

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29089 AN: 67960

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.424 Hom.: 4667

Bravo AF: 0.374

Asia WGS AF: 0.541 AC: 1883 AN: 3478

EpiCase AF: 0.440

EpiControl AF: 0.434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.3
DANN	Benign	0.81
PhyloP100		0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3736855; hg19: chr9-123917020; COSMIC: COSV53046956; COSMIC: COSV53046956;