11-72004706-G-T

Variant names:

• chr11-72004706-G-T
• rs1305351499
• NM_006185.4:c.5940C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_006185.4(NUMA1):​c.5940C>A​(p.Gly1980Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUMA1 NM_006185.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.234
• Publications: 0 publications found

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]

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.147).
• BP6: Variant 11-72004706-G-T is Benign according to our data. Variant chr11-72004706-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3047738.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006185.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	NM_006185.4	MANE Select	c.5940C>A	p.Gly1980Gly	synonymous	Exon 24 of 27	NP_006176.2	Q14980-1
	NUMA1	NM_001286561.2		c.5898C>A	p.Gly1966Gly	synonymous	Exon 24 of 27	NP_001273490.1	Q14980-2
	NUMA1	NR_104476.2		n.2857C>A		non_coding_transcript_exon	Exon 22 of 25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.5940C>A	p.Gly1980Gly	synonymous	Exon 24 of 27	ENSP00000377298.4	Q14980-1
	NUMA1	ENST00000351960.10	TSL:1	c.2532C>A	p.Gly844Gly	synonymous	Exon 22 of 25	ENSP00000260051.8	Q14980-5
	NUMA1	ENST00000541584.5	TSL:1	c.2484C>A	p.Gly828Gly	synonymous	Exon 10 of 13	ENSP00000440954.1	H0YFY6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NUMA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.84
DANN	Benign	0.84
PhyloP100		-0.23

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

Other links and lift over

dbSNP: rs1305351499; hg19: chr11-71715752;