rs1675126

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001040694.2(INCENP):c.1188T>C(p.Asn396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,613,082 control chromosomes in the GnomAD database, including 639,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.88 ( 59570 hom., cov: 33)

Exomes 𝑓: 0.89 ( 580142 hom. )

Consequence

INCENP
NM_001040694.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.62

Variant links:

Genes affected

INCENP (HGNC:6058): (inner centromere protein) In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger,' or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle (Earnshaw and Mackay, 1994 [PubMed 8088460]). These include CENPE (MIM 117143); MCAK (MIM 604538); KID (MIM 603213); cytoplasmic dynein (e.g., MIM 600112); CliPs (e.g., MIM 179838); and CENPF/mitosin (MIM 600236). The inner centromere proteins (INCENPs) (Earnshaw and Cooke, 1991 [PubMed 1860899]), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis (Cutts et al., 1999 [PubMed 10369859]).[supplied by OMIM, Mar 2008]

INCENP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 11-62138902-T-C is Benign according to our data. Variant chr11-62138902-T-C is described in ClinVar as [Benign]. Clinvar id is 1261519.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INCENP	NM_001040694.2 linkuse as main transcript	c.1188T>C	p.Asn396=	synonymous_variant	7/19	ENST00000394818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INCENP	ENST00000394818.8 linkuse as main transcript	c.1188T>C	p.Asn396=	synonymous_variant	7/19	1	NM_001040694.2	P2	Q9NQS7-1
INCENP	ENST00000278849.4 linkuse as main transcript	c.1188T>C	p.Asn396=	synonymous_variant	7/18	5		A2	Q9NQS7-2
INCENP	ENST00000528375.1 linkuse as main transcript	n.157T>C		non_coding_transcript_exon_variant	4/8	3

Frequencies

GnomAD3 genomes

AF:

0.879

AC:

133634

AN:

152082

Hom.:

59517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.904

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.945

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.912

Gnomad OTH

AF:

0.906

GnomAD3 exomes

AF:

0.842

AC:

211370

AN:

251046

Hom.:

91209

AF XY:

0.839

AC XY:

113950

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.906

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.950

Gnomad EAS exome

AF:

0.456

Gnomad SAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.913

Gnomad OTH exome

AF:

0.888

GnomAD4 exome

AF:

0.886

AC:

1294621

AN:

1460880

Hom.:

580142

Cov.:

AF XY:

0.882

AC XY:

641334

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.907

Gnomad4 AMR exome

AF:

0.898

Gnomad4 ASJ exome

AF:

0.947

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.917

Gnomad4 OTH exome

AF:

0.878

GnomAD4 genome

AF:

0.879

AC:

133746

AN:

152202

Hom.:

59570

Cov.:

AF XY:

0.866

AC XY:

64438

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.904

Gnomad4 AMR

AF:

0.929

Gnomad4 ASJ

AF:

0.945

Gnomad4 EAS

AF:

0.467

Gnomad4 SAS

AF:

0.719

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.912

Gnomad4 OTH

AF:

0.906

Alfa

AF:

0.914

Hom.:

77898

Bravo

AF:

0.894

Asia WGS

AF:

0.652

AC:

2271

AN:

3478

EpiCase

AF:

0.922

EpiControl

AF:

0.925

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

0.11

Dann

Benign

0.23

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over