chr19-2242830-A-C

Variant names:

• chr19-2242830-A-C
• rs7249235
• NM_007165.5:c.-37-552A>C

Variant summary

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

The NM_007165.5(SF3A2):​c.-37-552A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,072 control chromosomes in the GnomAD database, including 55,571 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 0.85 (55571 hom., cov: 31)
• Consequence: SF3A2 NM_007165.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3A2	NM_007165.5	c.-37-552A>C		intron_variant	Intron 1 of 8	ENST00000221494.10	NP_009096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3A2	ENST00000221494.10	c.-37-552A>C		intron_variant	Intron 1 of 8	1	NM_007165.5	ENSP00000221494.3

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129332 AN: 151954 Hom.: 55552 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.875

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.851 AC: 129400 AN: 152072 Hom.: 55571 Cov.: 31 AF XY: 0.852 AC XY: 63381 AN XY: 74400

African (AFR) AF: 0.743 AC: 30768 AN: 41434

American (AMR) AF: 0.822 AC: 12556 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3184 AN: 3472

East Asian (EAS) AF: 0.775 AC: 3999 AN: 5158

South Asian (SAS) AF: 0.904 AC: 4360 AN: 4824

European-Finnish (FIN) AF: 0.898 AC: 9518 AN: 10604

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62097 AN: 67986

Other (OTH) AF: 0.868 AC: 1833 AN: 2112

Alfa AF: 0.887 Hom.: 204869

Bravo AF: 0.836

Asia WGS AF: 0.806 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.046
DANN	Benign	0.30
PhyloP100		-1.7
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: rs7249235; hg19: chr19-2242829;