chr11-72019260-C-T

Variant names:

• chr11-72019260-C-T
• rs949326
• NM_006185.4:c.584+234G>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.584+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,240 control chromosomes in the GnomAD database, including 64,144 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 (64144 hom., cov: 31)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941
• Publications: 5 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]

ENSG00000251143 (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 = 0.969 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.584+234G>A		intron	N/A	NP_006176.2
	NUMA1	NM_001286561.2		c.584+234G>A		intron	N/A	NP_001273490.1
	NUMA1-AS1	NR_104178.2		n.3648+251C>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.584+234G>A		intron	N/A	ENSP00000377298.4
	NUMA1	ENST00000351960.10	TSL:1	c.584+234G>A		intron	N/A	ENSP00000260051.8
	NUMA1	ENST00000537217.5	TSL:1	c.584+234G>A		intron	N/A	ENSP00000442936.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139317 AN: 152122 Hom.: 64111 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.916 AC: 139407 AN: 152240 Hom.: 64144 Cov.: 31 AF XY: 0.912 AC XY: 67879 AN XY: 74448

African (AFR) AF: 0.836 AC: 34728 AN: 41520

American (AMR) AF: 0.853 AC: 13053 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3316 AN: 3472

East Asian (EAS) AF: 0.841 AC: 4349 AN: 5172

South Asian (SAS) AF: 0.882 AC: 4253 AN: 4824

European-Finnish (FIN) AF: 0.957 AC: 10159 AN: 10620

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66366 AN: 68018

Other (OTH) AF: 0.940 AC: 1988 AN: 2114

Alfa AF: 0.950 Hom.: 44863

Bravo AF: 0.908

Asia WGS AF: 0.870 AC: 3024 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	0.92
DANN	Benign	0.39
PhyloP100		-0.94
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: rs949326; hg19: chr11-71730306;