11-62127972-AG-A

Position:

• chr11-62127972-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001040694.2(INCENP):​c.-11-175del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (379 hom., cov: 0)
• Consequence: INCENP NM_001040694.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-62127972-AG-A is Benign according to our data. Variant chr11-62127972-AG-A is described in ClinVar as [Benign]. Clinvar id is 1272951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INCENP	NM_001040694.2	c.-11-175del		intron_variant		ENST00000394818.8	NP_001035784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INCENP	ENST00000394818.8	c.-11-175del		intron_variant		1	NM_001040694.2	ENSP00000378295	P2
INCENP	ENST00000528037.1	n.154-175del		intron_variant, non_coding_transcript_variant		1
INCENP	ENST00000278849.4	c.-11-175del		intron_variant		5		ENSP00000278849	A2
INCENP	ENST00000533896.5	c.-11-175del		intron_variant		4		ENSP00000433100

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 6069 AN: 60844 Hom.: 379 Cov.: 0

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.00957

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00413

Gnomad OTH AF: 0.0783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0998 AC: 6073 AN: 60874 Hom.: 379 Cov.: 0 AF XY: 0.0995 AC XY: 2854 AN XY: 28670

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0477

Gnomad4 ASJ AF: 0.00957

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00413

Gnomad4 OTH AF: 0.0783

Alfa AF: 0.0329 Hom.: 24

Bravo AF: 0.0447

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs368598822; hg19: chr11-61895444;