rs1057992

Positions:

• chr11-72016376-A-C
• chr11-72016376-A-G
• chr11-72016376-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006185.4(NUMA1):​c.1242+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 1,610,298 control chromosomes in the GnomAD database, including 746,947 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 0.94 (67557 hom., cov: 32)
  • Exomes 𝑓: 0.96 (679390 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

Genes affected

NUMA1 (HGNC:8059): (nuclear mitotic apparatus protein 1) This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUMA1	NM_006185.4	c.1242+32T>G		intron_variant		ENST00000393695.8
LOC100128494	NR_104178.1	n.2086A>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUMA1	ENST00000393695.8	c.1242+32T>G		intron_variant		1	NM_006185.4	P2
	ENST00000502284.1	n.2086A>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143139 AN: 152136 Hom.: 67508 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.959

GnomAD3 exomes AF: 0.938 AC: 233650 AN: 249104 Hom.: 109904 AF XY: 0.940 AC XY: 126533 AN XY: 134630

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.957

Gnomad EAS exome AF: 0.839

Gnomad SAS exome AF: 0.893

Gnomad FIN exome AF: 0.964

Gnomad NFE exome AF: 0.978

Gnomad OTH exome AF: 0.953

GnomAD4 exome AF: 0.965 AC: 1406506 AN: 1458044 Hom.: 679390 Cov.: 56 AF XY: 0.963 AC XY: 698356 AN XY: 725148

Gnomad4 AFR exome AF: 0.916

Gnomad4 AMR exome AF: 0.884

Gnomad4 ASJ exome AF: 0.959

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.894

Gnomad4 FIN exome AF: 0.967

Gnomad4 NFE exome AF: 0.980

Gnomad4 OTH exome AF: 0.958

GnomAD4 genome AF: 0.941 AC: 143246 AN: 152254 Hom.: 67557 Cov.: 32 AF XY: 0.936 AC XY: 69685 AN XY: 74454

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.960

Alfa AF: 0.973 Hom.: 68470

Bravo AF: 0.935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1057992; hg19: chr11-71727422; COSMIC: COSV61186494; COSMIC: COSV61186494;