2-230244614-T-C

Variant names:

• chr2-230244614-T-C
• rs6743984
• NM_007237.5:c.572-374T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007237.5(SP140):​c.572-374T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,056 control chromosomes in the GnomAD database, including 3,649 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 0.21 (3649 hom., cov: 32)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP140	NM_007237.5	c.572-374T>C		intron_variant	Intron 5 of 26	ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.572-374T>C		intron_variant	Intron 5 of 26	2	NM_007237.5	ENSP00000375899.3
SP140	ENST00000420434.7	c.572-374T>C		intron_variant	Intron 5 of 25	1		ENSP00000398210.3
SP140	ENST00000343805.10	c.572-374T>C		intron_variant	Intron 5 of 24	1		ENSP00000342096.6
SP140	ENST00000417495.7	c.572-374T>C		intron_variant	Intron 5 of 23	1		ENSP00000393618.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31506 AN: 151938 Hom.: 3638 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31553 AN: 152056 Hom.: 3649 Cov.: 32 AF XY: 0.202 AC XY: 15007 AN XY: 74336

African (AFR) AF: 0.312 AC: 12903 AN: 41414

American (AMR) AF: 0.154 AC: 2353 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.157 AC: 759 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10572

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12937 AN: 67982

Other (OTH) AF: 0.198 AC: 418 AN: 2112

Alfa AF: 0.202 Hom.: 1332

Bravo AF: 0.211

Asia WGS AF: 0.0780 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.45
PhyloP100		-0.90
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: rs6743984; hg19: chr2-231109329;