rs6716753

Variant names:

• chr2-230232414-T-C
• rs6716753
• NM_007237.5:c.60-4669T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-230232414-T-C
• chr2-230232414-T-G

Variant summary

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

The NM_007237.5(SP140):​c.60-4669T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,232 control chromosomes in the GnomAD database, including 2,408 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 0.17 (2408 hom., cov: 33)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 51 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 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.60-4669T>C		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.60-4669T>C		intron	N/A	NP_001265380.1
	SP140	NM_001278452.2		c.60-4669T>C		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.60-4669T>C		intron	N/A	ENSP00000375899.3
	SP140	ENST00000420434.7	TSL:1	c.60-4669T>C		intron	N/A	ENSP00000398210.3
	SP140	ENST00000343805.10	TSL:1	c.60-4669T>C		intron	N/A	ENSP00000342096.6

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26446 AN: 152114 Hom.: 2407 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.174 AC: 26453 AN: 152232 Hom.: 2408 Cov.: 33 AF XY: 0.169 AC XY: 12573 AN XY: 74418

African (AFR) AF: 0.191 AC: 7948 AN: 41526

American (AMR) AF: 0.141 AC: 2150 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3466

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

South Asian (SAS) AF: 0.163 AC: 785 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1397 AN: 10598

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13022 AN: 68014

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.177 Hom.: 3749

Bravo AF: 0.172

Asia WGS AF: 0.0700 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.44
PhyloP100		-0.085
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: rs6716753; hg19: chr2-231097129;