Genetic Variant NUMA1:c.461-52A>T (chr11-72019669-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.151

Publications

11 publications found

Variant links:

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]

NUMA1 links:

ENSG00000251143 (HGNC:58252):

ENSG00000251143 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUMA1	NM_006185.4 link	c.461-52A>T		intron_variant	Intron 8 of 26	ENST00000393695.8	NP_006176.2	Q14980-1Q3SYK8Q4LE64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8 link	c.461-52A>T		intron_variant	Intron 8 of 26	1	NM_006185.4	ENSP00000377298.4		Q14980-1

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134992

AN:

152142

Hom.:

60165

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.895

AC:

217759

AN:

243308

AF XY:

0.897

show subpopulations

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 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.:

AF XY:

0.927

AC XY:

661069

AN XY:

712966

show subpopulations

African (AFR)

AF:

0.815

AC:

26497

AN:

32502

American (AMR)

AF:

0.856

AC:

36155

AN:

42258

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

22863

AN:

25130

East Asian (EAS)

AF:

0.774

AC:

30068

AN:

38834

South Asian (SAS)

AF:

0.845

AC:

71096

AN:

84172

European-Finnish (FIN)

AF:

0.930

AC:

48206

AN:

51838

Middle Eastern (MID)

AF:

0.915

AC:

4776

AN:

5220

European-Non Finnish (NFE)

AF:

0.949

AC:

1040040

AN:

1096234

Other (OTH)

AF:

0.917

AC:

54085

AN:

58962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

4327

8654

12980

17307

21634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21466

42932

64398

85864

107330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.887

AC:

135080

AN:

152260

Hom.:

60195

Cov.:

AF XY:

0.882

AC XY:

65674

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.819

AC:

34012

AN:

41534

American (AMR)

AF:

0.828

AC:

12670

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3156

AN:

3470

East Asian (EAS)

AF:

0.766

AC:

3967

AN:

5176

South Asian (SAS)

AF:

0.839

AC:

4047

AN:

4822

European-Finnish (FIN)

AF:

0.932

AC:

9900

AN:

10620

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.945

AC:

64287

AN:

68014

Other (OTH)

AF:

0.907

AC:

1919

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

754

1508

2261

3015

3769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.44

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over