2-230211574-T-G

Variant names:

• chr2-230211574-T-G
• rs3820974
• NM_080424.4:c.668-21A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.668-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,472,124 control chromosomes in the GnomAD database, including 157,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18682 hom., cov: 30)
  • Exomes 𝑓: 0.45 (138527 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.53

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]

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 2-230211574-T-G is Benign according to our data. Variant chr2-230211574-T-G is described in ClinVar as [Benign]. Clinvar id is 1333151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.668-21A>C		intron_variant	Intron 5 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.668-21A>C		intron_variant	Intron 5 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74070 AN: 151570 Hom.: 18658 Cov.: 30

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.490 AC: 122953 AN: 250776 AF XY: 0.476

Gnomad AFR exome AF: 0.548

Gnomad AMR exome AF: 0.697

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.697

Gnomad FIN exome AF: 0.445

Gnomad NFE exome AF: 0.424

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.454 AC: 600072 AN: 1320436 Hom.: 138527 Cov.: 20 AF XY: 0.450 AC XY: 299264 AN XY: 664356

Gnomad4 AFR exome AF: 0.551 AC: 17006 AN: 30846

Gnomad4 AMR exome AF: 0.683 AC: 30421 AN: 44532

Gnomad4 ASJ exome AF: 0.417 AC: 10524 AN: 25258

Gnomad4 EAS exome AF: 0.697 AC: 27262 AN: 39112

Gnomad4 SAS exome AF: 0.419 AC: 34934 AN: 83344

Gnomad4 FIN exome AF: 0.441 AC: 23480 AN: 53274

Gnomad4 NFE exome AF: 0.436 AC: 428368 AN: 982824

Gnomad4 Remaining exome AF: 0.460 AC: 25629 AN: 55704

GnomAD4 genome AF: 0.489 AC: 74136 AN: 151688 Hom.: 18682 Cov.: 30 AF XY: 0.494 AC XY: 36624 AN XY: 74080

Gnomad4 AFR AF: 0.542 AC: 0.5425 AN: 0.5425

Gnomad4 AMR AF: 0.607 AC: 0.607316 AN: 0.607316

Gnomad4 ASJ AF: 0.422 AC: 0.421857 AN: 0.421857

Gnomad4 EAS AF: 0.706 AC: 0.706019 AN: 0.706019

Gnomad4 SAS AF: 0.416 AC: 0.416112 AN: 0.416112

Gnomad4 FIN AF: 0.458 AC: 0.458421 AN: 0.458421

Gnomad4 NFE AF: 0.427 AC: 0.426705 AN: 0.426705

Gnomad4 OTH AF: 0.497 AC: 0.496673 AN: 0.496673

Alfa AF: 0.457 Hom.: 7936

Bravo AF: 0.505

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.88
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: rs3820974; hg19: chr2-231076289; COSMIC: COSV51247617; COSMIC: COSV51247617;