dbSNP rs5743679: NUMA1:c.*540C>T (chr11-72002987-G-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.*540C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 234,954 control chromosomes in the GnomAD database, including 86 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 0.018 ( 79 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 7 hom. )

Consequence

NUMA1
NM_006185.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.283

Publications

3 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:

IL18BP (HGNC:5987): (interleukin 18 binding protein) The protein encoded by this gene functions as an inhibitor of the proinflammatory cytokine, IL18. It binds IL18, prevents the binding of IL18 to its receptor, and thus inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. This protein is constitutively expressed and secreted in mononuclear cells. Elevated level of this protein is detected in the intestinal tissues of patients with Crohn's disease. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

IL18BP Gene-Disease associations (from GenCC):

hepatitis, fulminant viral, susceptibility to
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IL18BP 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=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUMA1	NM_006185.4 link	c.*540C>T		3_prime_UTR_variant	Exon 27 of 27	ENST00000393695.8	NP_006176.2	Q14980-1Q3SYK8Q4LE64
IL18BP	NM_001039660.2 link	c.*1126G>A		downstream_gene_variant		ENST00000393703.9	NP_001034749.1	O95998-2A0A024R5G2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8 link	c.*540C>T		3_prime_UTR_variant	Exon 27 of 27	1	NM_006185.4	ENSP00000377298.4		Q14980-1
IL18BP	ENST00000393703.9 link	c.*1126G>A		downstream_gene_variant		3	NM_001039660.2	ENSP00000377306.4		O95998-2

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2693

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00876

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00957

GnomAD4 exome

AF:

0.00499

AC:

412

AN:

82632

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

183

AN XY:

38244

show subpopulations

African (AFR)

AF:

0.0652

AC:

253

AN:

3880

American (AMR)

AF:

0.00991

AC:

AN:

2624

Ashkenazi Jewish (ASJ)

AF:

0.00235

AC:

AN:

5100

East Asian (EAS)

AF:

0.00

AC:

AN:

11360

South Asian (SAS)

AF:

0.00

AC:

AN:

856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

530

Middle Eastern (MID)

AF:

0.00820

AC:

AN:

488

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

50978

Other (OTH)

AF:

0.00748

AC:

AN:

6816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0178

AC:

2705

AN:

152322

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1231

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0593

AC:

2464

AN:

41570

American (AMR)

AF:

0.00875

AC:

134

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68026

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00740

Hom.:

Bravo

AF:

0.0203

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.1

(source)

DANN

Benign

0.80

PhyloP100

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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