rs4820008

Positions:

• chr22-30353352-G-C
• chr22-30353352-G-T

Variant summary

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

The NM_005877.6(SF3A1):​c.64-280C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,226 control chromosomes in the GnomAD database, including 58,668 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 (58668 hom., cov: 31)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.97).
• 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.64-280C>G		intron_variant		ENST00000215793.13	NP_005868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A1	ENST00000215793.13	c.64-280C>G		intron_variant		1	NM_005877.6	ENSP00000215793	P1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133117 AN: 152110 Hom.: 58610 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.722

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: 0.813

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.875 AC: 133231 AN: 152226 Hom.: 58668 Cov.: 31 AF XY: 0.880 AC XY: 65477 AN XY: 74400

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: 0.813

Gnomad4 OTH AF: 0.879

Alfa AF: 0.845 Hom.: 6781

Bravo AF: 0.875

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.7
DANN	Benign	0.42

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: rs4820008; hg19: chr22-30749341;