2-230168917-A-ATTTTTTT

Variant names:

• chr2-230168917-A-ATTTTTTT
• rs1553839905
• NM_080424.4:c.*200_*206dupAAAAAAA

Variant summary

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

The NM_080424.4(SP110):​c.*200_*206dupAAAAAAA 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 0.0076 (18 hom., cov: 0)
  • Exomes 𝑓: 0.0045 (21 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), 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 = 0.00757 (1122/148142) while in subpopulation AFR AF = 0.0253 (1019/40324). AF 95% confidence interval is 0.024. There are 18 homozygotes in GnomAd4. There are 522 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.*200_*206dupAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.*200_*206dupAAAAAAA		3_prime_UTR_variant	Exon 19 of 19	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.00753 AC: 1115 AN: 148072 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00390

Gnomad ASJ AF: 0.00175

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00318

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000194

Gnomad OTH AF: 0.00442

GnomAD4 exome AF: 0.00448 AC: 1242 AN: 277356 Hom.: 21 Cov.: 0 AF XY: 0.00452 AC XY: 668 AN XY: 147834

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

African (AFR) AF: 0.00822 AC: 72 AN: 8758

American (AMR) AF: 0.00383 AC: 50 AN: 13050

Ashkenazi Jewish (ASJ) AF: 0.00410 AC: 34 AN: 8286

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

South Asian (SAS) AF: 0.00493 AC: 172 AN: 34870

European-Finnish (FIN) AF: 0.00290 AC: 43 AN: 14832

Middle Eastern (MID) AF: 0.0113 AC: 13 AN: 1146

European-Non Finnish (NFE) AF: 0.00488 AC: 782 AN: 160288

Other (OTH) AF: 0.00488 AC: 76 AN: 15570

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00757 AC: 1122 AN: 148142 Hom.: 18 Cov.: 0 AF XY: 0.00724 AC XY: 522 AN XY: 72050

African (AFR) AF: 0.0253 AC: 1019 AN: 40324

American (AMR) AF: 0.00396 AC: 59 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.00175 AC: 6 AN: 3434

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

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

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

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

European-Non Finnish (NFE) AF: 0.000194 AC: 13 AN: 67018

Other (OTH) AF: 0.00439 AC: 9 AN: 2052

Alfa AF: 0.00 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

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;