chr2-230365456-C-T

Variant names:

• chr2-230365456-C-T
• rs6712333
• NM_138402.6:c.523+3759C>T

Variant summary

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

The NM_138402.6(SP140L):​c.523+3759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,720 control chromosomes in the GnomAD database, including 7,643 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 0.27 (7643 hom., cov: 32)
• Consequence: SP140L NM_138402.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140L	NM_138402.6	MANE Select	c.523+3759C>T		intron	N/A	NP_612411.4
	SP140L	NM_001352892.2		c.523+3759C>T		intron	N/A	NP_001339821.1
	SP140L	NM_001308162.3		c.448+3759C>T		intron	N/A	NP_001295091.1	U5Y3L1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140L	ENST00000415673.7	TSL:5 MANE Select	c.523+3759C>T		intron	N/A	ENSP00000397911.2	Q9H930-4
	SP140L	ENST00000243810.10	TSL:1	c.448+3759C>T		intron	N/A	ENSP00000243810.7	U5Y3L1
	SP140L	ENST00000396563.8	TSL:1	c.448+3759C>T		intron	N/A	ENSP00000379811.5	H7BYP4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40518 AN: 151602 Hom.: 7610 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.268 AC: 40607 AN: 151720 Hom.: 7643 Cov.: 32 AF XY: 0.275 AC XY: 20355 AN XY: 74140

African (AFR) AF: 0.474 AC: 19612 AN: 41404

American (AMR) AF: 0.365 AC: 5558 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2922 AN: 5168

South Asian (SAS) AF: 0.358 AC: 1725 AN: 4818

European-Finnish (FIN) AF: 0.142 AC: 1489 AN: 10458

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8211 AN: 67846

Other (OTH) AF: 0.253 AC: 533 AN: 2108

Alfa AF: 0.162 Hom.: 1494

Bravo AF: 0.292

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.56
PhyloP100		0.14
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: rs6712333; hg19: chr2-231230171;