rs7153985

Variant names:

• chr14-69759770-T-C
• rs7153985
• ENST00000553521.5:c.-1161-6344T>C

Variant summary

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

The ENST00000553521.5(SRSF5):​c.-1161-6344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,166 control chromosomes in the GnomAD database, including 2,038 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 0.14 (2038 hom., cov: 32)
• Consequence: SRSF5 ENST00000553521.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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.-1161-6344T>C		intron_variant	Intron 1 of 8	1		ENSP00000452123.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21949 AN: 152048 Hom.: 2032 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.144 AC: 21985 AN: 152166 Hom.: 2038 Cov.: 32 AF XY: 0.144 AC XY: 10688 AN XY: 74412

African (AFR) AF: 0.260 AC: 10795 AN: 41476

American (AMR) AF: 0.155 AC: 2365 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3470

East Asian (EAS) AF: 0.155 AC: 804 AN: 5184

South Asian (SAS) AF: 0.134 AC: 648 AN: 4828

European-Finnish (FIN) AF: 0.0672 AC: 713 AN: 10618

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0916 AC: 6225 AN: 67990

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.105 Hom.: 1773

Bravo AF: 0.153

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.68
PhyloP100		-1.6
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: rs7153985; hg19: chr14-70226487;