chr2-230250915-A-T

Variant names:

• chr2-230250915-A-T
• rs9989835
• NM_007237.5:c.977-66A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007237.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	NM_007237.5	MANE Select	c.977-66A>T		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.977-66A>T		intron	N/A	NP_001265380.1
	SP140	NM_001278452.2		c.899-66A>T		intron	N/A	NP_001265381.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.977-66A>T		intron	N/A	ENSP00000375899.3
	SP140	ENST00000420434.7	TSL:1	c.977-66A>T		intron	N/A	ENSP00000398210.3
	SP140	ENST00000343805.10	TSL:1	c.899-66A>T		intron	N/A	ENSP00000342096.6

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

African (AFR) AF: 0.137 AC: 4465 AN: 32592

American (AMR) AF: 0.111 AC: 4856 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4618 AN: 25558

East Asian (EAS) AF: 0.00107 AC: 42 AN: 39396

South Asian (SAS) AF: 0.171 AC: 14483 AN: 84776

European-Finnish (FIN) AF: 0.125 AC: 6586 AN: 52680

Middle Eastern (MID) AF: 0.218 AC: 1233 AN: 5660

European-Non Finnish (NFE) AF: 0.187 AC: 201436 AN: 1077500

Other (OTH) AF: 0.167 AC: 9819 AN: 58854

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

African (AFR) AF: 0.135 AC: 5621 AN: 41516

American (AMR) AF: 0.131 AC: 2000 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 612 AN: 3462

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.157 AC: 755 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10600

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12580 AN: 67986

Other (OTH) AF: 0.156 AC: 330 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.51
PhyloP100		0.049
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

Other links and lift over

dbSNP: rs9989835; hg19: chr2-231115630;