chr11-72023165-T-C

Position:

• chr11-72023165-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393695.8(NUMA1):​c.209-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,591,008 control chromosomes in the GnomAD database, including 683,144 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 (60203 hom., cov: 31)
  • Exomes 𝑓: 0.93 (622941 hom.)
• Consequence: NUMA1 ENST00000393695.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.57).
• 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/exons	MANE	Protein	UniProt
NUMA1	NM_006185.4	c.209-18A>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.209-18A>G		intron_variant		1	NM_006185.4	ENSP00000377298	P2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134961 AN: 152034 Hom.: 60173 Cov.: 31

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.906

GnomAD3 exomes AF: 0.895 AC: 223893 AN: 250156 Hom.: 100651 AF XY: 0.897 AC XY: 121351 AN XY: 135298

Gnomad AFR exome AF: 0.819

Gnomad AMR exome AF: 0.862

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 0.760

Gnomad SAS exome AF: 0.846

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.943

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.929 AC: 1337182 AN: 1438856 Hom.: 622941 Cov.: 25 AF XY: 0.927 AC XY: 665123 AN XY: 717400

Gnomad4 AFR exome AF: 0.817

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.910

Gnomad4 EAS exome AF: 0.775

Gnomad4 SAS exome AF: 0.845

Gnomad4 FIN exome AF: 0.930

Gnomad4 NFE exome AF: 0.949

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.888 AC: 135049 AN: 152152 Hom.: 60203 Cov.: 31 AF XY: 0.883 AC XY: 65637 AN XY: 74366

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.908

Alfa AF: 0.925 Hom.: 32682

Bravo AF: 0.880

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	-0.57
CADD	Benign	11
DANN	Benign	0.87

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: rs2298457; hg19: chr11-71734211; COSMIC: COSV61183851; COSMIC: COSV61183851;