11-64772163-G-C

Variant names:

• chr11-64772163-G-C
• rs680273
• NM_004630.4:c.236+1267C>G

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SF1	NM_004630.4	c.236+1267C>G		intron_variant	Intron 3 of 12	ENST00000377390.8	NP_004621.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF1	ENST00000377390.8	c.236+1267C>G		intron_variant	Intron 3 of 12	1	NM_004630.4	ENSP00000366607.3

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 AC: 2512 AN: 15782

Gnomad4 AMR exome AF: 0.636 AC: 626 AN: 984

Gnomad4 ASJ exome AF: 0.843 AC: 4340 AN: 5150

Gnomad4 EAS exome AF: 0.643 AC: 2328 AN: 3622

Gnomad4 SAS exome AF: 0.835 AC: 13737 AN: 16456

Gnomad4 FIN exome AF: 0.895 AC: 247 AN: 276

Gnomad4 NFE exome AF: 0.907 AC: 690815 AN: 761728

Gnomad4 Remaining exome AF: 0.839 AC: 22885 AN: 27288

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 AC: 0.214944 AN: 0.214944

Gnomad4 AMR AF: 0.674 AC: 0.673828 AN: 0.673828

Gnomad4 ASJ AF: 0.849 AC: 0.849078 AN: 0.849078

Gnomad4 EAS AF: 0.633 AC: 0.633372 AN: 0.633372

Gnomad4 SAS AF: 0.817 AC: 0.816618 AN: 0.816618

Gnomad4 FIN AF: 0.889 AC: 0.888899 AN: 0.888899

Gnomad4 NFE AF: 0.897 AC: 0.89738 AN: 0.89738

Gnomad4 OTH AF: 0.721 AC: 0.721273 AN: 0.721273

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs680273; hg19: chr11-64539635;