2-230168917-A-ATTAATTT

Variant names:

• chr2-230168917-A-ATTAATTT
• rs5839361
• NM_080424.4:c.*206_*207insAAATTAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_080424.4(SP110):​c.*206_*207insAAATTAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 0)
  • Exomes 𝑓: 0.023 (24 hom.)
• Consequence: SP110 NM_080424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hepatic veno-occlusive disease-immunodeficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0012 (178/148148) while in subpopulation SAS AF = 0.00318 (15/4712). AF 95% confidence interval is 0.00196. There are 1 homozygotes in GnomAd4. There are 79 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. 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
	SP110	NM_080424.4	MANE Select	c.*206_*207insAAATTAA		3_prime_UTR	Exon 19 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.*206_*207insAAATTAA		3_prime_UTR	Exon 20 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.*206_*207insAAATTAA		3_prime_UTR	Exon 19 of 19	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.*206_*207insAAATTAA		3_prime_UTR	Exon 19 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.*206_*207insAAATTAA		3_prime_UTR	Exon 18 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.*206_*207insAAATTAA		splice_region	Exon 19 of 19	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 178 AN: 148082 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000873

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000590

Gnomad SAS AF: 0.00318

Gnomad FIN AF: 0.00127

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000492

GnomAD4 exome AF: 0.0228 AC: 6314 AN: 276538 Hom.: 24 Cov.: 0 AF XY: 0.0227 AC XY: 3354 AN XY: 147438

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0151 AC: 132 AN: 8730

American (AMR) AF: 0.0149 AC: 194 AN: 13028

Ashkenazi Jewish (ASJ) AF: 0.0221 AC: 183 AN: 8272

East Asian (EAS) AF: 0.0125 AC: 255 AN: 20478

South Asian (SAS) AF: 0.0231 AC: 802 AN: 34710

European-Finnish (FIN) AF: 0.0219 AC: 323 AN: 14770

Middle Eastern (MID) AF: 0.0245 AC: 28 AN: 1142

European-Non Finnish (NFE) AF: 0.0253 AC: 4045 AN: 159862

Other (OTH) AF: 0.0226 AC: 352 AN: 15546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00120 AC: 178 AN: 148148 Hom.: 1 Cov.: 0 AF XY: 0.00110 AC XY: 79 AN XY: 72044

African (AFR) AF: 0.00136 AC: 55 AN: 40354

American (AMR) AF: 0.000872 AC: 13 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3432

East Asian (EAS) AF: 0.000592 AC: 3 AN: 5068

South Asian (SAS) AF: 0.00318 AC: 15 AN: 4712

European-Finnish (FIN) AF: 0.00127 AC: 12 AN: 9446

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.00115 AC: 77 AN: 67008

Other (OTH) AF: 0.000488 AC: 1 AN: 2048

Alfa AF: 0.00 Hom.: 612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5839361; hg19: chr2-231033633;