NM_022909.4:c.190+497G>A

Variant names:

• chr5-69192347-G-A
• rs100192
• NM_022909.4:c.190+497G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022909.4(CENPH):​c.190+497G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,862 control chromosomes in the GnomAD database, including 12,905 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (12905 hom., cov: 31)
• Consequence: CENPH NM_022909.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 12 publications found

Genes affected

CENPH (HGNC:17268): (centromere protein H) Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. It localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022909.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPH	NM_022909.4	MANE Select	c.190+497G>A		intron	N/A	NP_075060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPH	ENST00000283006.7	TSL:1 MANE Select	c.190+497G>A		intron	N/A	ENSP00000283006.2
	CENPH	ENST00000515001.5	TSL:2	c.190+497G>A		intron	N/A	ENSP00000426014.1
	CENPH	ENST00000952160.1		c.190+497G>A		intron	N/A	ENSP00000622219.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62283 AN: 151744 Hom.: 12890 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.410 AC: 62334 AN: 151862 Hom.: 12905 Cov.: 31 AF XY: 0.414 AC XY: 30751 AN XY: 74212

African (AFR) AF: 0.375 AC: 15531 AN: 41412

American (AMR) AF: 0.444 AC: 6765 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.456 AC: 2357 AN: 5166

South Asian (SAS) AF: 0.554 AC: 2668 AN: 4814

European-Finnish (FIN) AF: 0.390 AC: 4113 AN: 10534

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28062 AN: 67924

Other (OTH) AF: 0.402 AC: 849 AN: 2110

Alfa AF: 0.412 Hom.: 15731

Bravo AF: 0.408

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs100192; hg19: chr5-68488174; COSMIC: COSV51584395; COSMIC: COSV51584395;