rs10493067

chr1-35186362-G-Achr1-35186362-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005066.3(SFPQ):c.1986+639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,080 control chromosomes in the GnomAD database, including 8,536 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 (8536 hom., cov: 32)
• Consequence: SFPQ NM_005066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

Genes affected

SFPQ (HGNC:10774): (splicing factor proline and glutamine rich) Enables DNA binding activity; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including alternative mRNA splicing, via spliceosome; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; and regulation of transcription by RNA polymerase II. Acts upstream of or within double-strand break repair via homologous recombination. Located in chromatin; nuclear matrix; and paraspeckles. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFPQ	NM_005066.3	c.1986+639C>T		intron_variant		ENST00000357214.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFPQ	ENST00000357214.6	c.1986+639C>T		intron_variant		1	NM_005066.3	P1
SFPQ	ENST00000696553.1	c.2049+639C>T		intron_variant
SFPQ	ENST00000460428.5	c.241+639C>T		intron_variant, NMD_transcript_variant		2
SFPQ	ENST00000470472.5	c.648+639C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34789 AN: 151962 Hom.: 8504 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.229 AC: 34889 AN: 152080 Hom.: 8536 Cov.: 32 AF XY: 0.235 AC XY: 17451 AN XY: 74348

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.203

Alfa AF: 0.0593 Hom.: 1652

Bravo AF: 0.263

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs10493067; hg19: chr1-35651963;