Genetic Variant NM_080424.4:c.317-706C>T (chr2-230213733-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080424.4(SP110):c.317-706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,632 control chromosomes in the GnomAD database, including 63,984 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 0.91 ( 63864 hom., cov: 33)

Exomes 𝑓: 0.81 ( 120 hom. )

Consequence

SP110
NM_080424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Publications

7 publications found

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 links:

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

SP140 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.317-706C>T		intron_variant	Intron 3 of 18	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.317-706C>T		intron_variant	Intron 3 of 18	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.915

AC:

139202

AN:

152160

Hom.:

63811

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.879

Gnomad AMR

AF:

0.917

Gnomad ASJ

AF:

0.925

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.867

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.911

GnomAD4 exome

AF:

0.814

AC:

288

AN:

354

Hom.:

120

Cov.:

AF XY:

0.804

AC XY:

156

AN XY:

194

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.875

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.900

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.796

AC:

234

AN:

294

Other (OTH)

AF:

0.929

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.915

AC:

139313

AN:

152278

Hom.:

63864

Cov.:

AF XY:

0.916

AC XY:

68171

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.972

AC:

40410

AN:

41570

American (AMR)

AF:

0.918

AC:

14046

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.925

AC:

3211

AN:

3472

East Asian (EAS)

AF:

0.997

AC:

5155

AN:

5168

South Asian (SAS)

AF:

0.942

AC:

4544

AN:

4822

European-Finnish (FIN)

AF:

0.867

AC:

9196

AN:

10604

Middle Eastern (MID)

AF:

0.921

AC:

269

AN:

292

European-Non Finnish (NFE)

AF:

0.879

AC:

59759

AN:

68022

Other (OTH)

AF:

0.910

AC:

1921

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

591

1182

1774

2365

2956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.900

Hom.:

16427

Bravo

AF:

0.921

Asia WGS

AF:

0.961

AC:

3342

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.3

(source)

DANN

Benign

0.40

PhyloP100

0.025

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_080424.4:c.317-706C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over