rs2298456

Variant names:

• chr11-72019669-T-A
• rs2298456
• NM_006185.4:c.461-52A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-72019669-T-A
• chr11-72019669-T-C
• chr11-72019669-T-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.461-52A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,587,410 control chromosomes in the GnomAD database, including 681,562 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 (60195 hom., cov: 32)
  • Exomes 𝑓: 0.93 (621367 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 11 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]

NUMA1-AS1 (HGNC:58252):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	NM_006185.4	MANE Select	c.461-52A>T		intron	N/A	NP_006176.2	Q14980-1
	NUMA1	NM_001286561.2		c.461-52A>T		intron	N/A	NP_001273490.1	Q14980-2
	NUMA1-AS1	NR_104178.2		n.3649-657T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.461-52A>T		intron	N/A	ENSP00000377298.4	Q14980-1
	NUMA1	ENST00000351960.10	TSL:1	c.461-52A>T		intron	N/A	ENSP00000260051.8	Q14980-5
	NUMA1	ENST00000537217.5	TSL:1	c.461-52A>T		intron	N/A	ENSP00000442936.1	F5H6Y5

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134992 AN: 152142 Hom.: 60165 Cov.: 32

Gnomad AFR AF: 0.819

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: 0.905

GnomAD2 exomes AF: 0.895 AC: 217759 AN: 243308 AF XY: 0.897

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 0.761

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.943

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.929 AC: 1333786 AN: 1435150 Hom.: 621367 Cov.: 25 AF XY: 0.927 AC XY: 661069 AN XY: 712966

African (AFR) AF: 0.815 AC: 26497 AN: 32502

American (AMR) AF: 0.856 AC: 36155 AN: 42258

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 22863 AN: 25130

East Asian (EAS) AF: 0.774 AC: 30068 AN: 38834

South Asian (SAS) AF: 0.845 AC: 71096 AN: 84172

European-Finnish (FIN) AF: 0.930 AC: 48206 AN: 51838

Middle Eastern (MID) AF: 0.915 AC: 4776 AN: 5220

European-Non Finnish (NFE) AF: 0.949 AC: 1040040 AN: 1096234

Other (OTH) AF: 0.917 AC: 54085 AN: 58962

GnomAD4 genome AF: 0.887 AC: 135080 AN: 152260 Hom.: 60195 Cov.: 32 AF XY: 0.882 AC XY: 65674 AN XY: 74448

African (AFR) AF: 0.819 AC: 34012 AN: 41534

American (AMR) AF: 0.828 AC: 12670 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3156 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3967 AN: 5176

South Asian (SAS) AF: 0.839 AC: 4047 AN: 4822

European-Finnish (FIN) AF: 0.932 AC: 9900 AN: 10620

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

European-Non Finnish (NFE) AF: 0.945 AC: 64287 AN: 68014

Other (OTH) AF: 0.907 AC: 1919 AN: 2116

Alfa AF: 0.919 Hom.: 11341

Bravo AF: 0.880

Asia WGS AF: 0.822 AC: 2856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.44
PhyloP100		0.15
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: rs2298456; hg19: chr11-71730715; COSMIC: COSV61192631; COSMIC: COSV61192631;