11-72036382-C-T

Variant names:

• chr11-72036382-C-T
• rs1573502
• NM_006185.4:c.-32-407G>A

Variant summary

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

The NM_006185.4(NUMA1):​c.-32-407G>A 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 152,300 control chromosomes in the GnomAD database, including 60,058 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 (60058 hom., cov: 34)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 2 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=-0.9).
• 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	c.-32-407G>A		intron_variant	Intron 2 of 26	ENST00000393695.8	NP_006176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.-32-407G>A		intron_variant	Intron 2 of 26	1	NM_006185.4	ENSP00000377298.4

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134834 AN: 152182 Hom.: 60027 Cov.: 34

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.886 AC: 134923 AN: 152300 Hom.: 60058 Cov.: 34 AF XY: 0.881 AC XY: 65607 AN XY: 74466

African (AFR) AF: 0.815 AC: 33856 AN: 41566

American (AMR) AF: 0.827 AC: 12649 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3158 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3972 AN: 5176

South Asian (SAS) AF: 0.840 AC: 4051 AN: 4824

European-Finnish (FIN) AF: 0.932 AC: 9897 AN: 10618

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

European-Non Finnish (NFE) AF: 0.945 AC: 64305 AN: 68038

Other (OTH) AF: 0.905 AC: 1911 AN: 2112

Alfa AF: 0.910 Hom.: 9538

Bravo AF: 0.878

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	-0.90
CADD	Benign	9.3
DANN	Benign	0.49
PhyloP100		0.41
PromoterAI		-0.0026	Neutral
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: rs1573502; hg19: chr11-71747428;