11-72037100-C-A

Variant names:

• chr11-72037100-C-A
• rs4945426
• NM_006185.4:c.-32-1125G>T

Variant summary

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

The NM_006185.4(NUMA1):​c.-32-1125G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,222 control chromosomes in the GnomAD database, including 60,024 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 (60024 hom., cov: 32)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	NM_006185.4	MANE Select	c.-32-1125G>T		intron	N/A	NP_006176.2
	NUMA1	NM_001286561.2		c.-32-1125G>T		intron	N/A	NP_001273490.1
	NUMA1	NR_104476.2		n.294-1125G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.-32-1125G>T		intron	N/A	ENSP00000377298.4
	NUMA1	ENST00000351960.10	TSL:1	c.-32-1125G>T		intron	N/A	ENSP00000260051.8
	NUMA1	ENST00000537217.5	TSL:1	c.-32-1125G>T		intron	N/A	ENSP00000442936.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134764 AN: 152104 Hom.: 59993 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.902

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.886 AC: 134853 AN: 152222 Hom.: 60024 Cov.: 32 AF XY: 0.881 AC XY: 65569 AN XY: 74420

African (AFR) AF: 0.815 AC: 33814 AN: 41504

American (AMR) AF: 0.828 AC: 12646 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3157 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3973 AN: 5182

South Asian (SAS) AF: 0.839 AC: 4053 AN: 4828

European-Finnish (FIN) AF: 0.932 AC: 9890 AN: 10610

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64286 AN: 68028

Other (OTH) AF: 0.904 AC: 1910 AN: 2112

Alfa AF: 0.905 Hom.: 19544

Bravo AF: 0.878

Asia WGS AF: 0.822 AC: 2857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

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: rs4945426; hg19: chr11-71748146;