rs1057992

Variant names:

• chr11-72016376-A-C
• rs1057992
• NM_006185.4:c.1242+32T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-72016376-A-C
• chr11-72016376-A-G
• chr11-72016376-A-T

Variant summary

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

The NM_006185.4(NUMA1):​c.1242+32T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 1,610,298 control chromosomes in the GnomAD database, including 746,947 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 0.94 (67557 hom., cov: 32)
  • Exomes 𝑓: 0.96 (679390 hom.)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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):

LOC100128494 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUMA1	NM_006185.4	c.1242+32T>G		intron_variant	Intron 14 of 26	ENST00000393695.8	NP_006176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.1242+32T>G		intron_variant	Intron 14 of 26	1	NM_006185.4	ENSP00000377298.4

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143139 AN: 152136 Hom.: 67508 Cov.: 32

Gnomad AFR AF: 0.917

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.959

GnomAD2 exomes AF: 0.938 AC: 233650 AN: 249104 AF XY: 0.940

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.957

Gnomad EAS exome AF: 0.839

Gnomad FIN exome AF: 0.964

Gnomad NFE exome AF: 0.978

Gnomad OTH exome AF: 0.953

GnomAD4 exome AF: 0.965 AC: 1406506 AN: 1458044 Hom.: 679390 Cov.: 56 AF XY: 0.963 AC XY: 698356 AN XY: 725148

Gnomad4 AFR exome AF: 0.916 AC: 30587 AN: 33386

Gnomad4 AMR exome AF: 0.884 AC: 39359 AN: 44526

Gnomad4 ASJ exome AF: 0.959 AC: 24787 AN: 25860

Gnomad4 EAS exome AF: 0.840 AC: 33327 AN: 39664

Gnomad4 SAS exome AF: 0.894 AC: 76810 AN: 85888

Gnomad4 FIN exome AF: 0.967 AC: 51552 AN: 53288

Gnomad4 NFE exome AF: 0.980 AC: 1087544 AN: 1110200

Gnomad4 Remaining exome AF: 0.958 AC: 57664 AN: 60212

GnomAD4 genome AF: 0.941 AC: 143246 AN: 152254 Hom.: 67557 Cov.: 32 AF XY: 0.936 AC XY: 69685 AN XY: 74454

Gnomad4 AFR AF: 0.917 AC: 0.916687 AN: 0.916687

Gnomad4 AMR AF: 0.861 AC: 0.861235 AN: 0.861235

Gnomad4 ASJ AF: 0.957 AC: 0.956797 AN: 0.956797

Gnomad4 EAS AF: 0.844 AC: 0.844113 AN: 0.844113

Gnomad4 SAS AF: 0.886 AC: 0.885714 AN: 0.885714

Gnomad4 FIN AF: 0.965 AC: 0.964683 AN: 0.964683

Gnomad4 NFE AF: 0.979 AC: 0.978646 AN: 0.978646

Gnomad4 OTH AF: 0.960 AC: 0.959754 AN: 0.959754

Alfa AF: 0.968 Hom.: 89227

Bravo AF: 0.935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs1057992; hg19: chr11-71727422; COSMIC: COSV61186494; COSMIC: COSV61186494;