rs9989835

Positions:

• chr2-230250915-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007237.5(SP140):​c.977-66A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,573,142 control chromosomes in the GnomAD database, including 24,867 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 0.15 (1924 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22943 hom.)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140	NM_007237.5	c.977-66A>T		intron_variant		ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.977-66A>T		intron_variant		2	NM_007237.5	ENSP00000375899	A2
SP140	ENST00000343805.10	c.899-66A>T		intron_variant		1		ENSP00000342096	A2
SP140	ENST00000417495.7	c.817+1947A>T		intron_variant		1		ENSP00000393618	P2
SP140	ENST00000420434.7	c.977-66A>T		intron_variant		1		ENSP00000398210	A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23355 AN: 152064 Hom.: 1921 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.174 AC: 247538 AN: 1420960 Hom.: 22943 AF XY: 0.175 AC XY: 124007 AN XY: 708536

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.00107

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.154 AC: 23370 AN: 152182 Hom.: 1924 Cov.: 32 AF XY: 0.149 AC XY: 11074 AN XY: 74420

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.156

Alfa AF: 0.170 Hom.: 287

Bravo AF: 0.150

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.51

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: rs9989835; hg19: chr2-231115630;