11-72004172-T-C

Variant names:

• chr11-72004172-T-C
• rs2852365
• NM_006185.4:c.6123+53A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006185.4(NUMA1):​c.6123+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 1,606,634 control chromosomes in the GnomAD database, including 740,794 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 0.92 (65075 hom., cov: 35)
  • Exomes 𝑓: 0.96 (675719 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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	c.6123+53A>G		intron_variant	Intron 25 of 26	ENST00000393695.8	NP_006176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.6123+53A>G		intron_variant	Intron 25 of 26	1	NM_006185.4	ENSP00000377298.4

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140317 AN: 152022 Hom.: 65042 Cov.: 35

Gnomad AFR AF: 0.854

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.978

Gnomad OTH AF: 0.945

GnomAD4 exome AF: 0.963 AC: 1400800 AN: 1454494 Hom.: 675719 Cov.: 34 AF XY: 0.962 AC XY: 696073 AN XY: 723860

African (AFR) AF: 0.851 AC: 27971 AN: 32882

American (AMR) AF: 0.881 AC: 37486 AN: 42542

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 24798 AN: 25870

East Asian (EAS) AF: 0.840 AC: 33315 AN: 39642

South Asian (SAS) AF: 0.894 AC: 76741 AN: 85804

European-Finnish (FIN) AF: 0.967 AC: 51596 AN: 53336

Middle Eastern (MID) AF: 0.970 AC: 5539 AN: 5712

European-Non Finnish (NFE) AF: 0.980 AC: 1086101 AN: 1108704

Other (OTH) AF: 0.954 AC: 57253 AN: 60002

GnomAD4 genome AF: 0.923 AC: 140408 AN: 152140 Hom.: 65075 Cov.: 35 AF XY: 0.919 AC XY: 68314 AN XY: 74366

African (AFR) AF: 0.854 AC: 35414 AN: 41486

American (AMR) AF: 0.856 AC: 13091 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3320 AN: 3470

East Asian (EAS) AF: 0.845 AC: 4361 AN: 5158

South Asian (SAS) AF: 0.886 AC: 4275 AN: 4826

European-Finnish (FIN) AF: 0.965 AC: 10227 AN: 10602

Middle Eastern (MID) AF: 0.973 AC: 284 AN: 292

European-Non Finnish (NFE) AF: 0.978 AC: 66527 AN: 67992

Other (OTH) AF: 0.946 AC: 1997 AN: 2110

Alfa AF: 0.950 Hom.: 8767

Bravo AF: 0.916

Asia WGS AF: 0.879 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2852365; hg19: chr11-71715218;