NM_006185.4:c.-32-760C>G

Variant names:

• chr11-72036735-G-C
• rs7127865
• NM_006185.4:c.-32-760C>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.-32-760C>G 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 152,188 control chromosomes in the GnomAD database, including 60,012 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 (60012 hom., cov: 31)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 3 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=-0.82).
• 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.-32-760C>G		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.-32-760C>G		intron_variant	Intron 2 of 26	1	NM_006185.4	ENSP00000377298.4

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134732 AN: 152070 Hom.: 59981 Cov.: 31

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.839

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: 134821 AN: 152188 Hom.: 60012 Cov.: 31 AF XY: 0.881 AC XY: 65561 AN XY: 74408

African (AFR) AF: 0.814 AC: 33795 AN: 41492

American (AMR) AF: 0.828 AC: 12643 AN: 15278

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

East Asian (EAS) AF: 0.767 AC: 3963 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4047 AN: 4824

European-Finnish (FIN) AF: 0.932 AC: 9888 AN: 10610

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

European-Non Finnish (NFE) AF: 0.945 AC: 64293 AN: 68026

Other (OTH) AF: 0.904 AC: 1912 AN: 2114

Alfa AF: 0.908 Hom.: 3021

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	-0.82
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7127865; hg19: chr11-71747781;