11-62128004-G-A

Position:

• chr11-62128004-G-A

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.-11-147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 694,420 control chromosomes in the GnomAD database, including 23,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4449 hom., cov: 31)
  • Exomes 𝑓: 0.25 (19040 hom.)
• Consequence: INCENP NM_001040694.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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=-0.83).
• BP6: Variant 11-62128004-G-A is Benign according to our data. Variant chr11-62128004-G-A is described in ClinVar as [Benign]. Clinvar id is 1179975.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INCENP	NM_001040694.2	c.-11-147G>A		intron_variant		ENST00000394818.8	NP_001035784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INCENP	ENST00000394818.8	c.-11-147G>A		intron_variant		1	NM_001040694.2	ENSP00000378295	P2
INCENP	ENST00000528037.1	n.154-147G>A		intron_variant, non_coding_transcript_variant		1
INCENP	ENST00000278849.4	c.-11-147G>A		intron_variant		5		ENSP00000278849	A2
INCENP	ENST00000533896.5	c.-11-147G>A		intron_variant		4		ENSP00000433100

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35014 AN: 151728 Hom.: 4448 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.254 AC: 137617 AN: 542574 Hom.: 19040 AF XY: 0.252 AC XY: 72883 AN XY: 288862

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.231 AC: 35026 AN: 151846 Hom.: 4449 Cov.: 31 AF XY: 0.227 AC XY: 16812 AN XY: 74200

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0778

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.230

Alfa AF: 0.242 Hom.: 1477

Bravo AF: 0.219

Asia WGS AF: 0.146 AC: 510 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	-0.83
CADD	Benign	14
DANN	Benign	0.67

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: rs3825035; hg19: chr11-61895476;