chr14-69733746-G-A

Variant names:

• chr14-69733746-G-A
• rs8007929
• ENST00000553521.5:c.-1162+6555G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF5	ENST00000553521.5	c.-1162+6555G>A		intron_variant	Intron 1 of 8	1		ENSP00000452123.1

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

African (AFR) AF: 0.0754 AC: 3132 AN: 41524

American (AMR) AF: 0.0941 AC: 1439 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5166

South Asian (SAS) AF: 0.124 AC: 599 AN: 4822

European-Finnish (FIN) AF: 0.0732 AC: 776 AN: 10608

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7906 AN: 68012

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.115 Hom.: 3188

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
PhyloP100		1.0
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: rs8007929; hg19: chr14-70200463;