11-62128069-A-G

Position:

• chr11-62128069-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040694.2(INCENP):​c.-11-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 1,401,322 control chromosomes in the GnomAD database, including 282,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (25784 hom., cov: 31)
  • Exomes 𝑓: 0.62 (256923 hom.)
• Consequence: INCENP NM_001040694.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-62128069-A-G is Benign according to our data. Variant chr11-62128069-A-G is described in ClinVar as [Benign]. Clinvar id is 1221642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INCENP	NM_001040694.2	c.-11-82A>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.-11-82A>G		intron_variant		1	NM_001040694.2	ENSP00000378295.3
INCENP	ENST00000528037.1	n.154-82A>G		intron_variant		1
INCENP	ENST00000278849.4	c.-11-82A>G		intron_variant		5		ENSP00000278849.4
INCENP	ENST00000533896.5	c.-11-82A>G		intron_variant		4		ENSP00000433100.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85285 AN: 151766 Hom.: 25781 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.622 AC: 777370 AN: 1249438 Hom.: 256923 AF XY: 0.614 AC XY: 384682 AN XY: 626300

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.687

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.562 AC: 85311 AN: 151884 Hom.: 25784 Cov.: 31 AF XY: 0.548 AC XY: 40680 AN XY: 74224

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.599

Alfa AF: 0.621 Hom.: 3810

Bravo AF: 0.549

Asia WGS AF: 0.253 AC: 888 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.89
CADD	Benign	3.0
DANN	Benign	0.44

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: rs1675130; hg19: chr11-61895541; COSMIC: COSV53913526; COSMIC: COSV53913526;