rs100192

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPH	NM_022909.4	c.190+497G>A		intron_variant	Intron 2 of 8	ENST00000283006.7	NP_075060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPH	ENST00000283006.7	c.190+497G>A		intron_variant	Intron 2 of 8	1	NM_022909.4	ENSP00000283006.2

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.402

Alfa AF: 0.411 Hom.: 13024

Bravo AF: 0.408

Asia WGS AF: 0.519 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.38

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