rs3744061

Positions:

• chr17-76737321-G-A
• chr17-76737321-G-C

Variant summary

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

The NM_001195427.2(SRSF2):​c.-161C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 973,052 control chromosomes in the GnomAD database, including 138,841 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 0.42 (16105 hom., cov: 35)
  • Exomes 𝑓: 0.54 (122736 hom.)
• Consequence: SRSF2 NM_001195427.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) 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. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRSF2	NM_001195427.2	c.-161C>T		5_prime_UTR_variant	1/3	ENST00000359995.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRSF2	ENST00000359995.10	c.-161C>T		5_prime_UTR_variant	1/3	1	NM_001195427.2	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63381 AN: 152060 Hom.: 16107 Cov.: 35

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.538 AC: 441886 AN: 820874 Hom.: 122736 Cov.: 10 AF XY: 0.536 AC XY: 218436 AN XY: 407648

Gnomad4 AFR exome AF: 0.0924

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.568

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.416 AC: 63371 AN: 152178 Hom.: 16105 Cov.: 35 AF XY: 0.415 AC XY: 30830 AN XY: 74366

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.434

Alfa AF: 0.539 Hom.: 26271

Bravo AF: 0.402

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.99
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3744061; hg19: chr17-74733403;