22-30342598-T-C

Variant names:

• chr22-30342598-T-C
• rs2074733
• NM_005877.6:c.726+207A>G

Variant summary

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

The NM_005877.6(SF3A1):​c.726+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 621,584 control chromosomes in the GnomAD database, including 81,767 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 0.53 (21378 hom., cov: 31)
  • Exomes 𝑓: 0.50 (60389 hom.)
• Consequence: SF3A1 NM_005877.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 18 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3A1	NM_005877.6	c.726+207A>G		intron_variant	Intron 5 of 15	ENST00000215793.13	NP_005868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3A1	ENST00000215793.13	c.726+207A>G		intron_variant	Intron 5 of 15	1	NM_005877.6	ENSP00000215793.7
SF3A1	ENST00000471037.1	n.504A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
SF3A1	ENST00000411423.1	n.64-3419A>G		intron_variant	Intron 1 of 3	4		ENSP00000412715.1
SF3A1	ENST00000447376.1	n.*68+207A>G		intron_variant	Intron 3 of 3	5		ENSP00000397267.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80048 AN: 151780 Hom.: 21358 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.505 AC: 237111 AN: 469682 Hom.: 60389 Cov.: 5 AF XY: 0.506 AC XY: 125316 AN XY: 247682

African (AFR) AF: 0.598 AC: 7623 AN: 12746

American (AMR) AF: 0.511 AC: 9619 AN: 18824

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 8934 AN: 13890

East Asian (EAS) AF: 0.416 AC: 13065 AN: 31392

South Asian (SAS) AF: 0.524 AC: 23677 AN: 45204

European-Finnish (FIN) AF: 0.424 AC: 13029 AN: 30724

Middle Eastern (MID) AF: 0.548 AC: 1141 AN: 2082

European-Non Finnish (NFE) AF: 0.507 AC: 145919 AN: 288014

Other (OTH) AF: 0.526 AC: 14104 AN: 26806

GnomAD4 genome AF: 0.527 AC: 80121 AN: 151902 Hom.: 21378 Cov.: 31 AF XY: 0.523 AC XY: 38777 AN XY: 74212

African (AFR) AF: 0.595 AC: 24624 AN: 41412

American (AMR) AF: 0.526 AC: 8033 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2241 AN: 3462

East Asian (EAS) AF: 0.453 AC: 2335 AN: 5158

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4816

European-Finnish (FIN) AF: 0.430 AC: 4525 AN: 10530

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34186 AN: 67936

Other (OTH) AF: 0.544 AC: 1146 AN: 2108

Alfa AF: 0.521 Hom.: 44397

Bravo AF: 0.541

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.49
PhyloP100		-1.8
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: rs2074733; hg19: chr22-30738587; COSMIC: COSV53171898; COSMIC: COSV53171898;