chr19-57231699-C-G

Variant names:

• chr19-57231699-C-G
• rs2361127
• ENST00000598785.5:c.-87C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000598785.5(AURKC):​c.-87C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,609,416 control chromosomes in the GnomAD database, including 85,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8213 hom., cov: 28)
  • Exomes 𝑓: 0.32 (77038 hom.)
• Consequence: AURKC ENST00000598785.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.326
• Publications: 5 publications found

Genes affected

AURKC (HGNC:11391): (aurora kinase C) This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

AURKC Gene-Disease associations (from GenCC):

• spermatogenic failure 5

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-57231699-C-G is Benign according to our data. Variant chr19-57231699-C-G is described in ClinVar as [Benign]. Clinvar id is 1262537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AURKC	NM_001015878.2	c.59-43C>G		intron_variant	Intron 1 of 6	ENST00000302804.12	NP_001015878.1
AURKC	NM_001015879.2	c.2-43C>G		intron_variant	Intron 1 of 6		NP_001015879.1
AURKC	NM_003160.3	c.-44-43C>G		intron_variant	Intron 1 of 6		NP_003151.2
AURKC	XM_047439253.1	c.59-43C>G		intron_variant	Intron 1 of 4		XP_047295209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AURKC	ENST00000302804.12	c.59-43C>G		intron_variant	Intron 1 of 6	1	NM_001015878.2	ENSP00000302898.6

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48041 AN: 150856 Hom.: 8204 Cov.: 28

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.352 AC: 87351 AN: 248296 AF XY: 0.348

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.298

Gnomad EAS exome AF: 0.695

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.316 AC: 461440 AN: 1458444 Hom.: 77038 Cov.: 34 AF XY: 0.317 AC XY: 229796 AN XY: 725678

African (AFR) AF: 0.307 AC: 10251 AN: 33404

American (AMR) AF: 0.410 AC: 18314 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 7929 AN: 26102

East Asian (EAS) AF: 0.689 AC: 27330 AN: 39680

South Asian (SAS) AF: 0.368 AC: 31680 AN: 86172

European-Finnish (FIN) AF: 0.336 AC: 17921 AN: 53392

Middle Eastern (MID) AF: 0.271 AC: 1563 AN: 5760

European-Non Finnish (NFE) AF: 0.294 AC: 326487 AN: 1109028

Other (OTH) AF: 0.331 AC: 19965 AN: 60286

GnomAD4 genome AF: 0.319 AC: 48093 AN: 150972 Hom.: 8213 Cov.: 28 AF XY: 0.323 AC XY: 23815 AN XY: 73698

African (AFR) AF: 0.307 AC: 12565 AN: 40984

American (AMR) AF: 0.352 AC: 5343 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1078 AN: 3460

East Asian (EAS) AF: 0.685 AC: 3459 AN: 5050

South Asian (SAS) AF: 0.382 AC: 1823 AN: 4774

European-Finnish (FIN) AF: 0.349 AC: 3646 AN: 10454

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19314 AN: 67796

Other (OTH) AF: 0.298 AC: 623 AN: 2092

Alfa AF: 0.290 Hom.: 1209

Bravo AF: 0.322

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-0.33
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2361127; hg19: chr19-57743067; COSMIC: COSV57136794; COSMIC: COSV57136794;