rs8007929

Positions:

• chr14-69733746-G-A

Variant summary

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

The ENST00000553521.5(SRSF5):​c.-1162+6555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,220 control chromosomes in the GnomAD database, including 978 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 0.10 (978 hom., cov: 32)
• Consequence: SRSF5 ENST00000553521.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

SRSF5 (HGNC:10787): (serine and arginine rich splicing factor 5) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF5	ENST00000553521.5	c.-1162+6555G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15982 AN: 152102 Hom.: 980 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0732

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.105 AC: 15981 AN: 152220 Hom.: 978 Cov.: 32 AF XY: 0.103 AC XY: 7699 AN XY: 74408

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0732

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.125

Alfa AF: 0.115 Hom.: 1486

Bravo AF: 0.106

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.86

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: rs8007929; hg19: chr14-70200463;