rs4820834

Positions:

• chr22-30355638-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.63+1092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,268 control chromosomes in the GnomAD database, including 817 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 0.090 (817 hom., cov: 32)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

SF3A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A1	NM_005877.6	c.63+1092C>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.63+1092C>T		intron_variant		1	NM_005877.6	ENSP00000215793.7

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13648 AN: 152150 Hom.: 816 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0903

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0896 AC: 13649 AN: 152268 Hom.: 817 Cov.: 32 AF XY: 0.0861 AC XY: 6410 AN XY: 74458

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.0903

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.111

Alfa AF: 0.117 Hom.: 306

Bravo AF: 0.0901

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.69

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: rs4820834; hg19: chr22-30751627;