11-64778919-C-T

Variant names:

• chr11-64778919-C-T
• rs606458
• ENST00000334944.9:c.-527G>A

Variant summary

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

The ENST00000334944.9(SF1):​c.-527G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 167,946 control chromosomes in the GnomAD database, including 48,517 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 0.71 (42967 hom., cov: 31)
  • Exomes 𝑓: 0.82 (5550 hom.)
• Consequence: SF1 ENST00000334944.9 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

Genes affected

SF1 (HGNC:12950): (splicing factor 1) This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3' splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

SF1-DT (HGNC:55278): (SF1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.892 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
SF1	ENST00000334944.9	c.-527G>A		upstream_gene_variant		1		ENSP00000334414.5
SF1	ENST00000377394.7	c.-527G>A		upstream_gene_variant		1		ENSP00000366611.3
SF1	ENST00000227503.13	c.-527G>A		upstream_gene_variant		1		ENSP00000227503.9

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108588 AN: 151914 Hom.: 42968 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.823 AC: 13095 AN: 15914 Hom.: 5550 Cov.: 0 AF XY: 0.827 AC XY: 6899 AN XY: 8346

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.839

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.723

Gnomad4 FIN exome AF: 0.876

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.714 AC: 108619 AN: 152032 Hom.: 42967 Cov.: 31 AF XY: 0.714 AC XY: 53053 AN XY: 74332

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.898

Gnomad4 OTH AF: 0.748

Alfa AF: 0.869 Hom.: 56831

Bravo AF: 0.684

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.9
DANN	Benign	0.81

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs606458; hg19: chr11-64546391;