11-72042099-G-C

Position:

• chr11-72042099-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMA1	NM_006185.4	c.-32-6124C>G		intron_variant		ENST00000393695.8	NP_006176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.-32-6124C>G		intron_variant		1	NM_006185.4	ENSP00000377298	P2

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

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.950

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.840

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.74

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: rs4945430; hg19: chr11-71753145;