rs5749066

Positions:

• chr22-30340922-G-A

Variant summary

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

The NM_005877.6(SF3A1):​c.1072-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 687,540 control chromosomes in the GnomAD database, including 251,474 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 0.88 (58698 hom., cov: 33)
  • Exomes 𝑓: 0.85 (192776 hom.)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

SF3A1 (HGNC:10765): (splicing factor 3a subunit 1) This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A1	NM_005877.6	c.1072-110C>T		intron_variant		ENST00000215793.13	NP_005868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A1	ENST00000215793.13	c.1072-110C>T		intron_variant		1	NM_005877.6	ENSP00000215793	P1
SF3A1	ENST00000444440.1	c.160-110C>T		intron_variant		5		ENSP00000400862
SF3A1	ENST00000411423.1	c.64-1743C>T		intron_variant, NMD_transcript_variant		4		ENSP00000412715

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133188 AN: 152196 Hom.: 58639 Cov.: 33

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.847 AC: 453474 AN: 535226 Hom.: 192776 AF XY: 0.850 AC XY: 243523 AN XY: 286332

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.891

Gnomad4 EAS exome AF: 0.910

Gnomad4 SAS exome AF: 0.920

Gnomad4 FIN exome AF: 0.874

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.859

GnomAD4 genome AF: 0.875 AC: 133304 AN: 152314 Hom.: 58698 Cov.: 33 AF XY: 0.880 AC XY: 65541 AN XY: 74472

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.880

Alfa AF: 0.845 Hom.: 6784

Bravo AF: 0.875

Asia WGS AF: 0.922 AC: 3208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.3
DANN	Benign	0.68

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: rs5749066; hg19: chr22-30736911;