NM_006185.4:c.-32-6124C>G

Variant names:

• chr11-72042099-G-C
• rs4945430
• NM_006185.4:c.-32-6124C>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.-32-6124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,228 control chromosomes in the GnomAD database, including 50,173 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 0.79 (50141 hom., cov: 32)
  • Exomes 𝑓: 0.93 (32 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 0 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 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.-32-6124C>G		intron	N/A	NP_006176.2
	NUMA1	NM_001286561.2		c.-32-6124C>G		intron	N/A	NP_001273490.1
	NUMA1	NR_104476.2		n.294-6124C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.-32-6124C>G		intron	N/A	ENSP00000377298.4
	NUMA1	ENST00000351960.10	TSL:1	c.-32-6124C>G		intron	N/A	ENSP00000260051.8
	NUMA1	ENST00000537217.5	TSL:1	c.-32-6124C>G		intron	N/A	ENSP00000442936.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119539 AN: 152036 Hom.: 50144 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.932 AC: 69 AN: 74 Hom.: 32 Cov.: 0 AF XY: 0.935 AC XY: 58 AN XY: 62

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.950 AC: 57 AN: 60

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.786 AC: 119557 AN: 152154 Hom.: 50141 Cov.: 32 AF XY: 0.786 AC XY: 58437 AN XY: 74388

African (AFR) AF: 0.469 AC: 19441 AN: 41444

American (AMR) AF: 0.787 AC: 12032 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3152 AN: 3472

East Asian (EAS) AF: 0.766 AC: 3955 AN: 5160

South Asian (SAS) AF: 0.838 AC: 4048 AN: 4832

European-Finnish (FIN) AF: 0.932 AC: 9889 AN: 10610

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64151 AN: 68028

Other (OTH) AF: 0.840 AC: 1775 AN: 2114

Alfa AF: 0.813 Hom.: 2982

Bravo AF: 0.764

Asia WGS AF: 0.793 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.74
PhyloP100		-0.23
PromoterAI		-0.027	Neutral
Mutation Taster		=99/1	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: rs4945430; hg19: chr11-71753145;