rs606458

Variant names:

• chr11-64778919-C-A
• rs606458
• ENST00000594089.2:n.21-28C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-64778919-C-A
• chr11-64778919-C-G
• chr11-64778919-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000594089.2(SF1-DT):​n.21-28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SF1-DT ENST00000594089.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 41 publications found

Genes affected

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

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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-DT	ENST00000594089.2	n.21-28C>A		intron_variant	Intron 1 of 1	6
SF1	ENST00000334944.9	c.-527G>T		upstream_gene_variant		1		ENSP00000334414.5
SF1	ENST00000377394.7	c.-527G>T		upstream_gene_variant		1		ENSP00000366611.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 15998 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8378

African (AFR) AF: 0.00 AC: 0 AN: 408

American (AMR) AF: 0.00 AC: 0 AN: 394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 580

East Asian (EAS) AF: 0.00 AC: 0 AN: 1638

South Asian (SAS) AF: 0.00 AC: 0 AN: 148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10110

Other (OTH) AF: 0.00 AC: 0 AN: 970

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 87385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		-0.29
PromoterAI		-0.00020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs606458; hg19: chr11-64546391;