11-64772163-G-C

Position:

• chr11-64772163-G-C

Variant summary

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

The NM_004630.4(SF1):​c.236+1267C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 985,000 control chromosomes in the GnomAD database, including 373,593 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 0.67 (41162 hom., cov: 31)
  • Exomes 𝑓: 0.89 (332431 hom.)
• Consequence: SF1 NM_004630.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.313

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF1	NM_004630.4	c.236+1267C>G		intron_variant		ENST00000377390.8	NP_004621.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF1	ENST00000377390.8	c.236+1267C>G		intron_variant		1	NM_004630.4	ENSP00000366607	A1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102448 AN: 151976 Hom.: 41169 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.887 AC: 738848 AN: 832906 Hom.: 332431 Cov.: 30 AF XY: 0.889 AC XY: 341940 AN XY: 384642

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.843

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.895

Gnomad4 NFE exome AF: 0.907

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.674 AC: 102452 AN: 152094 Hom.: 41162 Cov.: 31 AF XY: 0.675 AC XY: 50191 AN XY: 74348

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.721

Alfa AF: 0.692 Hom.: 2794

Bravo AF: 0.637

Asia WGS AF: 0.688 AC: 2391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs680273; hg19: chr11-64539635;