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
• Publications: 11 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004630.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF1	NM_004630.4	MANE Select	c.236+1267C>G		intron	N/A	NP_004621.2
	SF1	NM_001378957.1		c.611+1267C>G		intron	N/A	NP_001365886.1
	SF1	NM_001378956.1		c.611+1267C>G		intron	N/A	NP_001365885.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF1	ENST00000377390.8	TSL:1 MANE Select	c.236+1267C>G		intron	N/A	ENSP00000366607.3
	SF1	ENST00000377387.5	TSL:1	c.611+1267C>G		intron	N/A	ENSP00000366604.1
	SF1	ENST00000334944.9	TSL:1	c.236+1267C>G		intron	N/A	ENSP00000334414.5

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

African (AFR) AF: 0.159 AC: 2512 AN: 15782

American (AMR) AF: 0.636 AC: 626 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 4340 AN: 5150

East Asian (EAS) AF: 0.643 AC: 2328 AN: 3622

South Asian (SAS) AF: 0.835 AC: 13737 AN: 16456

European-Finnish (FIN) AF: 0.895 AC: 247 AN: 276

Middle Eastern (MID) AF: 0.838 AC: 1358 AN: 1620

European-Non Finnish (NFE) AF: 0.907 AC: 690815 AN: 761728

Other (OTH) 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

African (AFR) AF: 0.215 AC: 8909 AN: 41448

American (AMR) AF: 0.674 AC: 10288 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.633 AC: 3272 AN: 5166

South Asian (SAS) AF: 0.817 AC: 3941 AN: 4826

European-Finnish (FIN) AF: 0.889 AC: 9417 AN: 10594

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61029 AN: 68008

Other (OTH) AF: 0.721 AC: 1519 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		-0.31
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

Other links and lift over

dbSNP: rs680273; hg19: chr11-64539635;