dbSNP rs2298457: NUMA1:c.209-18A>G (chr11-72023165-T-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.209-18A>G 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 1,591,008 control chromosomes in the GnomAD database, including 683,144 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 ( 60203 hom., cov: 31)

Exomes 𝑓: 0.93 ( 622941 hom. )

Consequence

NUMA1
NM_006185.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0840

Publications

17 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:

Genome browser will be placed here

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=-0.57).

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.209-18A>G		intron_variant	Intron 5 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.209-18A>G		intron_variant	Intron 5 of 26	1	NM_006185.4	ENSP00000377298.4		Q14980-1

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

134961

AN:

152034

Hom.:

60173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.820

Gnomad AMI

AF:

0.943

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.767

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.945

Gnomad OTH

AF:

0.906

GnomAD2 exomes

AF:

0.895

AC:

223893

AN:

250156

AF XY:

0.897

show subpopulations

Gnomad AFR exome

AF:

0.819

Gnomad AMR exome

AF:

0.862

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

0.760

Gnomad FIN exome

AF:

0.926

Gnomad NFE exome

AF:

0.943

Gnomad OTH exome

AF:

0.913

GnomAD4 exome

AF:

0.929

AC:

1337182

AN:

1438856

Hom.:

622941

Cov.:

AF XY:

0.927

AC XY:

665123

AN XY:

717400

show subpopulations

African (AFR)

AF:

0.817

AC:

26950

AN:

32968

American (AMR)

AF:

0.857

AC:

38293

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

23654

AN:

25992

East Asian (EAS)

AF:

0.775

AC:

30659

AN:

39564

South Asian (SAS)

AF:

0.845

AC:

72487

AN:

85768

European-Finnish (FIN)

AF:

0.930

AC:

48424

AN:

52076

Middle Eastern (MID)

AF:

0.918

AC:

5252

AN:

5724

European-Non Finnish (NFE)

AF:

0.949

AC:

1036757

AN:

1092450

Other (OTH)

AF:

0.917

AC:

54706

AN:

59632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

4485

8970

13454

17939

22424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21054

42108

63162

84216

105270

<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:

0.888

AC:

135049

AN:

152152

Hom.:

60203

Cov.:

AF XY:

0.883

AC XY:

65637

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.820

AC:

33988

AN:

41464

American (AMR)

AF:

0.829

AC:

12668

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.910

AC:

3155

AN:

3468

East Asian (EAS)

AF:

0.767

AC:

3961

AN:

5164

South Asian (SAS)

AF:

0.840

AC:

4048

AN:

4818

European-Finnish (FIN)

AF:

0.932

AC:

9890

AN:

10606

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.945

AC:

64301

AN:

68030

Other (OTH)

AF:

0.908

AC:

1914

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.927

Hom.:

36098

Bravo

AF:

0.880

Asia WGS

AF:

0.822

AC:

2857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-0.084

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