Genetic Variant NUMA1:c.1242+32T>G (chr11-72016376-A-C) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

Publications

16 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=-0.93).

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 rank	MANE	Protein	UniProt
NUMA1	NM_006185.4 link	c.1242+32T>G		intron_variant	Intron 14 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.1242+32T>G		intron_variant	Intron 14 of 26	1	NM_006185.4	ENSP00000377298.4		Q14980-1

Frequencies

GnomAD3 genomes

AF:

0.941

AC:

143139

AN:

152136

Hom.:

67508

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.938

AC:

233650

AN:

249104

AF XY:

0.940

show subpopulations

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 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.:

AF XY:

0.963

AC XY:

698356

AN XY:

725148

show subpopulations

African (AFR)

AF:

0.916

AC:

30587

AN:

33386

American (AMR)

AF:

0.884

AC:

39359

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.959

AC:

24787

AN:

25860

East Asian (EAS)

AF:

0.840

AC:

33327

AN:

39664

South Asian (SAS)

AF:

0.894

AC:

76810

AN:

85888

European-Finnish (FIN)

AF:

0.967

AC:

51552

AN:

53288

Middle Eastern (MID)

AF:

0.971

AC:

4876

AN:

5020

European-Non Finnish (NFE)

AF:

0.980

AC:

1087544

AN:

1110200

Other (OTH)

AF:

0.958

AC:

57664

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

2733

5466

8198

10931

13664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21628

43256

64884

86512

108140

<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:

0.941

AC:

143246

AN:

152254

Hom.:

67557

Cov.:

AF XY:

0.936

AC XY:

69685

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.917

AC:

38059

AN:

41518

American (AMR)

AF:

0.861

AC:

13170

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.957

AC:

3322

AN:

3472

East Asian (EAS)

AF:

0.844

AC:

4359

AN:

5164

South Asian (SAS)

AF:

0.886

AC:

4278

AN:

4830

European-Finnish (FIN)

AF:

0.965

AC:

10243

AN:

10618

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.979

AC:

66589

AN:

68042

Other (OTH)

AF:

0.960

AC:

2027

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

429

858

1286

1715

2144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.968

Hom.:

89227

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

(source)

DANN

Benign

0.65

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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