chr2-230168917-A-ATTTTTT

Variant names:

• chr2-230168917-A-ATTTTTT
• rs1553839905
• NM_080424.4:c.*201_*206dupAAAAAA

Variant summary

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

The NM_080424.4(SP110):​c.*201_*206dupAAAAAA 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 0.00045 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: SP110 NM_080424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• Publications: 0 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 afr. GnomAd4 allele frequency = 0.000452 (67/148174) while in subpopulation AFR AF = 0.00151 (61/40356). AF 95% confidence interval is 0.00121. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.*201_*206dupAAAAAA		3_prime_UTR	Exon 19 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.*201_*206dupAAAAAA		3_prime_UTR	Exon 20 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.*201_*206dupAAAAAA		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.*201_*206dupAAAAAA		3_prime_UTR	Exon 19 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.*201_*206dupAAAAAA		3_prime_UTR	Exon 18 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.*201_*206dupAAAAAA		splice_region	Exon 19 of 19	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.000452 AC: 67 AN: 148104 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000672

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.000982

GnomAD4 exome AF: 0.00155 AC: 431 AN: 277646 Hom.: 5 Cov.: 0 AF XY: 0.00168 AC XY: 248 AN XY: 148014

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

African (AFR) AF: 0.00434 AC: 38 AN: 8756

American (AMR) AF: 0.00138 AC: 18 AN: 13082

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 9 AN: 8296

East Asian (EAS) AF: 0.00 AC: 0 AN: 20556

South Asian (SAS) AF: 0.00198 AC: 69 AN: 34888

European-Finnish (FIN) AF: 0.000741 AC: 11 AN: 14838

Middle Eastern (MID) AF: 0.00262 AC: 3 AN: 1146

European-Non Finnish (NFE) AF: 0.00157 AC: 252 AN: 160492

Other (OTH) AF: 0.00199 AC: 31 AN: 15592

⚠️ 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: 0.000452 AC: 67 AN: 148174 Hom.: 0 Cov.: 0 AF XY: 0.000430 AC XY: 31 AN XY: 72062

African (AFR) AF: 0.00151 AC: 61 AN: 40356

American (AMR) AF: 0.0000671 AC: 1 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5068

South Asian (SAS) AF: 0.00 AC: 0 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67018

Other (OTH) AF: 0.000975 AC: 2 AN: 2052

Alfa AF: 0.00 Hom.: 25

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: rs1553839905; hg19: chr2-231033633;