rs2233911

Positions:

• chr17-58006573-G-A
• chr17-58006573-G-C

Variant summary

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

The NM_006924.5(SRSF1):​c.195-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,556,788 control chromosomes in the GnomAD database, including 341,823 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 0.54 (26691 hom., cov: 34)
  • Exomes 𝑓: 0.66 (315132 hom.)
• Consequence: SRSF1 NM_006924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

SRSF1 (HGNC:10780): (serine and arginine rich splicing factor 1) This gene encodes a member of the arginine/serine-rich splicing factor protein family. The encoded protein can either activate or repress splicing, depending on its phosphorylation state and its interaction partners. Multiple transcript variants have been found for this gene. There is a pseudogene of this gene on chromosome 13. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF1	NM_006924.5	c.195-46C>T		intron_variant		ENST00000258962.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF1	ENST00000258962.5	c.195-46C>T		intron_variant		1	NM_006924.5	P1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82596 AN: 152110 Hom.: 26692 Cov.: 34

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.661 AC: 125225 AN: 189582 Hom.: 42992 AF XY: 0.668 AC XY: 68560 AN XY: 102608

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.765

Gnomad SAS exome AF: 0.684

Gnomad FIN exome AF: 0.765

Gnomad NFE exome AF: 0.678

Gnomad OTH exome AF: 0.668

GnomAD4 exome AF: 0.664 AC: 932788 AN: 1404560 Hom.: 315132 Cov.: 32 AF XY: 0.666 AC XY: 461271 AN XY: 692666

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.543 AC: 82591 AN: 152228 Hom.: 26691 Cov.: 34 AF XY: 0.554 AC XY: 41211 AN XY: 74420

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.588

Alfa AF: 0.654 Hom.: 71328

Bravo AF: 0.516

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.65
DANN	Benign	0.81

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: rs2233911; hg19: chr17-56083934; COSMIC: COSV51965750; COSMIC: COSV51965750;