Variant chr11-62129725-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040694.2(INCENP):c.255-57C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,415,840 control chromosomes in the GnomAD database, including 283,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23687 hom., cov: 31)

Exomes 𝑓: 0.62 ( 259315 hom. )

Consequence

INCENP
NM_001040694.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.258

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-62129725-C-T is Benign according to our data. Variant chr11-62129725-C-T is described in ClinVar as [Benign]. Clinvar id is 1181058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INCENP	NM_001040694.2 linkuse as main transcript	c.255-57C>T		intron_variant		ENST00000394818.8	NP_001035784.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
INCENP	ENST00000394818.8 linkuse as main transcript	c.255-57C>T	intron_variant	1	NM_001040694.2	ENSP00000378295	P2	Q9NQS7-1
INCENP	ENST00000528037.1 linkuse as main transcript	n.419-57C>T	intron_variant, non_coding_transcript_variant	1
INCENP	ENST00000278849.4 linkuse as main transcript	c.255-57C>T	intron_variant	5		ENSP00000278849	A2	Q9NQS7-2
INCENP	ENST00000533896.5 linkuse as main transcript	c.255-57C>T	intron_variant	4		ENSP00000433100

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80265

AN:

151794

Hom.:

23689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.705

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.577

GnomAD4 exome

AF:

0.622

AC:

785543

AN:

1263928

Hom.:

259315

AF XY:

0.613

AC XY:

384455

AN XY:

626766

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.329

Gnomad4 ASJ exome

AF:

0.714

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.528

AC:

80283

AN:

151912

Hom.:

23687

Cov.:

AF XY:

0.516

AC XY:

38310

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.347

Gnomad4 AMR

AF:

0.452

Gnomad4 ASJ

AF:

0.705

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.574

Alfa

AF:

0.597

Hom.:

4332

Bravo

AF:

0.510

Asia WGS

AF:

0.238

AC:

834

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.0

DANN

Benign

0.71

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