rs4807216

Variant names:

• chr19-2248684-C-T
• rs4807216
• NM_007165.5:c.*138C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007165.5(SF3A2):​c.*138C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 380,430 control chromosomes in the GnomAD database, including 122,508 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 0.76 (44897 hom., cov: 26)
  • Exomes 𝑓: 0.82 (77611 hom.)
• Consequence: SF3A2 NM_007165.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• Publications: 23 publications found

Genes affected

SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007165.5. 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
	SF3A2	NM_007165.5	MANE Select	c.*138C>T		downstream_gene	N/A	NP_009096.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	ENST00000221494.10	TSL:1 MANE Select	c.*138C>T		downstream_gene	N/A	ENSP00000221494.3

Frequencies

GnomAD3 genomes AF: 0.761 AC: 114843 AN: 150934 Hom.: 44899 Cov.: 26

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.791

GnomAD4 exome AF: 0.817 AC: 187323 AN: 229378 Hom.: 77611 Cov.: 2 AF XY: 0.818 AC XY: 94920 AN XY: 116014

African (AFR) AF: 0.583 AC: 3941 AN: 6758

American (AMR) AF: 0.716 AC: 5946 AN: 8302

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 7808 AN: 8824

East Asian (EAS) AF: 0.626 AC: 12137 AN: 19398

South Asian (SAS) AF: 0.788 AC: 3139 AN: 3982

European-Finnish (FIN) AF: 0.823 AC: 15085 AN: 18334

Middle Eastern (MID) AF: 0.852 AC: 1021 AN: 1198

European-Non Finnish (NFE) AF: 0.855 AC: 125901 AN: 147216

Other (OTH) AF: 0.803 AC: 12345 AN: 15366

GnomAD4 genome AF: 0.761 AC: 114878 AN: 151052 Hom.: 44897 Cov.: 26 AF XY: 0.760 AC XY: 56094 AN XY: 73806

African (AFR) AF: 0.581 AC: 23865 AN: 41094

American (AMR) AF: 0.759 AC: 11536 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3102 AN: 3468

East Asian (EAS) AF: 0.608 AC: 3065 AN: 5040

South Asian (SAS) AF: 0.799 AC: 3815 AN: 4774

European-Finnish (FIN) AF: 0.830 AC: 8720 AN: 10510

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58109 AN: 67658

Other (OTH) AF: 0.784 AC: 1648 AN: 2102

Alfa AF: 0.824 Hom.: 31213

Bravo AF: 0.742

Asia WGS AF: 0.651 AC: 2268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		-0.62
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4807216; hg19: chr19-2248683; COSMIC: COSV55557403;