1-35186362-G-A

Variant names:

• chr1-35186362-G-A
• rs10493067
• NM_005066.3:c.1986+639C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005066.3. 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
	SFPQ	NM_005066.3	MANE Select	c.1986+639C>T		intron	N/A	NP_005057.1
	SFPQ	NR_136702.2		n.2082+639C>T		intron	N/A
	SFPQ	NR_136703.2		n.2094+639C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFPQ	ENST00000357214.6	TSL:1 MANE Select	c.1986+639C>T		intron	N/A	ENSP00000349748.5
	SFPQ	ENST00000696553.1		c.2049+639C>T		intron	N/A	ENSP00000512713.1
	SFPQ	ENST00000460428.5	TSL:2	n.240+639C>T		intron	N/A	ENSP00000425071.1

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

African (AFR) AF: 0.552 AC: 22868 AN: 41444

American (AMR) AF: 0.300 AC: 4584 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.664 AC: 3440 AN: 5180

South Asian (SAS) AF: 0.142 AC: 683 AN: 4826

European-Finnish (FIN) AF: 0.117 AC: 1235 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0223 AC: 1516 AN: 67990

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.0816 Hom.: 3342

Bravo AF: 0.263

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.42
PhyloP100		0.52
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: rs10493067; hg19: chr1-35651963;