chr1-35180524-C-T

Variant names:

• chr1-35180524-C-T
• rs10493066
• ENST00000468598.5:n.122G>A

Variant summary

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

The ENST00000468598.5(SFPQ):​n.122G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 1,049,484 control chromosomes in the GnomAD database, including 16,290 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 (8834 hom., cov: 32)
  • Exomes 𝑓: 0.045 (7456 hom.)
• Consequence: SFPQ ENST00000468598.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• 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=-0.72).
• 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: ENST00000468598.5. 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
	SFPQ	NR_136702.2		n.2083-2488G>A		intron	N/A
	SFPQ	NR_136703.2		n.2095-2488G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFPQ	ENST00000468598.5	TSL:1	n.122G>A		non_coding_transcript_exon	Exon 1 of 3
	SFPQ	ENST00000460428.5	TSL:2	n.241-2488G>A		intron	N/A	ENSP00000425071.1
	SFPQ	ENST00000470472.5	TSL:5	n.649-2488G>A		intron	N/A	ENSP00000424440.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35301 AN: 151954 Hom.: 8799 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.0452 AC: 40535 AN: 897412 Hom.: 7456 Cov.: 33 AF XY: 0.0430 AC XY: 17826 AN XY: 414494

African (AFR) AF: 0.602 AC: 11287 AN: 18734

American (AMR) AF: 0.340 AC: 978 AN: 2880

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 314 AN: 9310

East Asian (EAS) AF: 0.695 AC: 9045 AN: 13018

South Asian (SAS) AF: 0.130 AC: 2217 AN: 17010

European-Finnish (FIN) AF: 0.0994 AC: 32 AN: 322

Middle Eastern (MID) AF: 0.0537 AC: 108 AN: 2012

European-Non Finnish (NFE) AF: 0.0165 AC: 13207 AN: 801402

Other (OTH) AF: 0.102 AC: 3347 AN: 32724

GnomAD4 genome AF: 0.233 AC: 35407 AN: 152072 Hom.: 8834 Cov.: 32 AF XY: 0.238 AC XY: 17689 AN XY: 74328

African (AFR) AF: 0.564 AC: 23359 AN: 41436

American (AMR) AF: 0.301 AC: 4603 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0346 AC: 120 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3431 AN: 5166

South Asian (SAS) AF: 0.141 AC: 678 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0224 AC: 1522 AN: 68012

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.0931 Hom.: 11958

Bravo AF: 0.266

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10493066; hg19: chr1-35646125;