2-230372858-T-C

Variant names:

• chr2-230372858-T-C
• rs1074886
• NM_138402.6:c.637+1207T>C

Variant summary

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

The NM_138402.6(SP140L):​c.637+1207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 150,102 control chromosomes in the GnomAD database, including 4,798 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 0.23 (4798 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: SP140L NM_138402.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 5 publications found

Genes affected

SP140L (HGNC:25105): (SP140 nuclear body protein like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138402.6. 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
	SP140L	NM_138402.6	MANE Select	c.637+1207T>C		intron	N/A	NP_612411.4
	SP140L	NM_001352892.2		c.637+1207T>C		intron	N/A	NP_001339821.1
	SP140L	NM_001308162.3		c.562+1207T>C		intron	N/A	NP_001295091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140L	ENST00000415673.7	TSL:5 MANE Select	c.637+1207T>C		intron	N/A	ENSP00000397911.2
	SP140L	ENST00000243810.10	TSL:1	c.562+1207T>C		intron	N/A	ENSP00000243810.7
	SP140L	ENST00000396563.8	TSL:1	c.562+1207T>C		intron	N/A	ENSP00000379811.5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34753 AN: 149984 Hom.: 4794 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.232 AC: 34766 AN: 150096 Hom.: 4798 Cov.: 32 AF XY: 0.236 AC XY: 17271 AN XY: 73232

African (AFR) AF: 0.0988 AC: 4004 AN: 40522

American (AMR) AF: 0.199 AC: 2985 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3464

East Asian (EAS) AF: 0.0696 AC: 354 AN: 5084

South Asian (SAS) AF: 0.230 AC: 1093 AN: 4760

European-Finnish (FIN) AF: 0.391 AC: 4008 AN: 10254

Middle Eastern (MID) AF: 0.250 AC: 72 AN: 288

European-Non Finnish (NFE) AF: 0.304 AC: 20553 AN: 67712

Other (OTH) AF: 0.250 AC: 517 AN: 2070

Alfa AF: 0.281 Hom.: 4854

Bravo AF: 0.208

Asia WGS AF: 0.197 AC: 688 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	4.6
DANN	Benign	0.60
PhyloP100		0.15
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: rs1074886; hg19: chr2-231237573;