chr11-62129117-T-G

Position:

• chr11-62129117-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040694.2(INCENP):​c.254+234T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,800 control chromosomes in the GnomAD database, including 23,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (23708 hom., cov: 32)
• Consequence: INCENP NM_001040694.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.110

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-62129117-T-G is Benign according to our data. Variant chr11-62129117-T-G is described in ClinVar as [Benign]. Clinvar id is 1282557.Status of the report is criteria_provided_single_submitter, 1 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	c.254+234T>G		intron_variant		ENST00000394818.8	NP_001035784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INCENP	ENST00000394818.8	c.254+234T>G		intron_variant		1	NM_001040694.2	ENSP00000378295	P2
INCENP	ENST00000528037.1	n.418+234T>G		intron_variant, non_coding_transcript_variant		1
INCENP	ENST00000278849.4	c.254+234T>G		intron_variant		5		ENSP00000278849	A2
INCENP	ENST00000533896.5	c.254+234T>G		intron_variant		4		ENSP00000433100

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80334 AN: 151682 Hom.: 23710 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.529 AC: 80352 AN: 151800 Hom.: 23708 Cov.: 32 AF XY: 0.517 AC XY: 38339 AN XY: 74152

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.574

Alfa AF: 0.481 Hom.: 1537

Bravo AF: 0.510

Asia WGS AF: 0.238 AC: 835 AN: 3478

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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.54

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: rs1675132; hg19: chr11-61896589;