rs2298456

Positions:

• chr11-72019669-T-A
• chr11-72019669-T-C
• chr11-72019669-T-G

Variant summary

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

The NM_006185.4(NUMA1):​c.461-52A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,587,410 control chromosomes in the GnomAD database, including 681,562 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 0.89 (60195 hom., cov: 32)
  • Exomes 𝑓: 0.93 (621367 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMA1	NM_006185.4	c.461-52A>T		intron_variant		ENST00000393695.8	NP_006176.2
LOC100128494	NR_104178.1	n.3649-657T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.461-52A>T		intron_variant		1	NM_006185.4	ENSP00000377298	P2
	ENST00000502284.1	n.3649-657T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134992 AN: 152142 Hom.: 60165 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.905

GnomAD3 exomes AF: 0.895 AC: 217759 AN: 243308 Hom.: 97891 AF XY: 0.897 AC XY: 118270 AN XY: 131834

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 0.761

Gnomad SAS exome AF: 0.845

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.943

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.929 AC: 1333786 AN: 1435150 Hom.: 621367 Cov.: 25 AF XY: 0.927 AC XY: 661069 AN XY: 712966

Gnomad4 AFR exome AF: 0.815

Gnomad4 AMR exome AF: 0.856

Gnomad4 ASJ exome AF: 0.910

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.845

Gnomad4 FIN exome AF: 0.930

Gnomad4 NFE exome AF: 0.949

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.887 AC: 135080 AN: 152260 Hom.: 60195 Cov.: 32 AF XY: 0.882 AC XY: 65674 AN XY: 74448

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.907

Alfa AF: 0.919 Hom.: 11341

Bravo AF: 0.880

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.44

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: rs2298456; hg19: chr11-71730715; COSMIC: COSV61192631; COSMIC: COSV61192631;