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
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.972 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.1242+32T>G		intron	N/A	NP_006176.2	Q14980-1
	NUMA1	NM_001286561.2		c.1242+32T>G		intron	N/A	NP_001273490.1	Q14980-2
	NUMA1-AS1	NR_104178.2		n.2086A>C		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMA1	ENST00000393695.8	TSL:1 MANE Select	c.1242+32T>G		intron	N/A	ENSP00000377298.4	Q14980-1
	NUMA1	ENST00000351960.10	TSL:1	c.1242+32T>G		intron	N/A	ENSP00000260051.8	Q14980-5
	NUMA1	ENST00000537217.5	TSL:1	c.1242+32T>G		intron	N/A	ENSP00000442936.1	F5H6Y5

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

African (AFR) AF: 0.916 AC: 30587 AN: 33386

American (AMR) AF: 0.884 AC: 39359 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 24787 AN: 25860

East Asian (EAS) AF: 0.840 AC: 33327 AN: 39664

South Asian (SAS) AF: 0.894 AC: 76810 AN: 85888

European-Finnish (FIN) AF: 0.967 AC: 51552 AN: 53288

Middle Eastern (MID) AF: 0.971 AC: 4876 AN: 5020

European-Non Finnish (NFE) AF: 0.980 AC: 1087544 AN: 1110200

Other (OTH) 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

African (AFR) AF: 0.917 AC: 38059 AN: 41518

American (AMR) AF: 0.861 AC: 13170 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3322 AN: 3472

East Asian (EAS) AF: 0.844 AC: 4359 AN: 5164

South Asian (SAS) AF: 0.886 AC: 4278 AN: 4830

European-Finnish (FIN) AF: 0.965 AC: 10243 AN: 10618

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66589 AN: 68042

Other (OTH) AF: 0.960 AC: 2027 AN: 2112

Alfa AF: 0.968 Hom.: 89227

Bravo AF: 0.935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-0.16
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

Other links and lift over

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