rs2233911

Variant names:

• chr17-58006573-G-A
• rs2233911
• NM_006924.5:c.195-46C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

SRSF1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Baylor College of Medicine Research Center

ENSG00000266086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006924.5. 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
	SRSF1	NM_006924.5	MANE Select	c.195-46C>T		intron	N/A	NP_008855.1
	SRSF1	NM_001078166.2		c.195-46C>T		intron	N/A	NP_001071634.1
	SRSF1	NR_034041.2		n.304-46C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF1	ENST00000258962.5	TSL:1 MANE Select	c.195-46C>T		intron	N/A	ENSP00000258962.4
	ENSG00000266086	ENST00000578794.2	TSL:3	n.195-46C>T		intron	N/A	ENSP00000463235.2
	SRSF1	ENST00000581979.5	TSL:1	n.195-46C>T		intron	N/A	ENSP00000463223.1

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

GnomAD2 exomes AF: 0.661 AC: 125225 AN: 189582 AF XY: 0.668

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 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

African (AFR) AF: 0.138 AC: 4418 AN: 31974

American (AMR) AF: 0.688 AC: 25130 AN: 36520

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 15300 AN: 24126

East Asian (EAS) AF: 0.733 AC: 27651 AN: 37716

South Asian (SAS) AF: 0.682 AC: 55139 AN: 80872

European-Finnish (FIN) AF: 0.763 AC: 38196 AN: 50032

Middle Eastern (MID) AF: 0.588 AC: 2963 AN: 5040

European-Non Finnish (NFE) AF: 0.672 AC: 726270 AN: 1080272

Other (OTH) AF: 0.650 AC: 37721 AN: 58008

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

African (AFR) AF: 0.167 AC: 6951 AN: 41542

American (AMR) AF: 0.665 AC: 10169 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2189 AN: 3472

East Asian (EAS) AF: 0.770 AC: 3980 AN: 5168

South Asian (SAS) AF: 0.675 AC: 3259 AN: 4826

European-Finnish (FIN) AF: 0.762 AC: 8077 AN: 10594

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46027 AN: 68006

Other (OTH) AF: 0.588 AC: 1242 AN: 2112

Alfa AF: 0.628 Hom.: 98290

Bravo AF: 0.516

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.65
DANN	Benign	0.81
PhyloP100		-1.2
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: rs2233911; hg19: chr17-56083934; COSMIC: COSV51965750; COSMIC: COSV51965750;