rs788018

Variant names:

• chr2-197400802-A-G
• rs788018
• NM_012433.4:c.2631T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-197400802-A-G
• chr2-197400802-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012433.4(SF3B1):​c.2631T>C​(p.Gly877Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,611,526 control chromosomes in the GnomAD database, including 375,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38925 hom., cov: 31)
  • Exomes 𝑓: 0.68 (336277 hom.)
• Consequence: SF3B1 NM_012433.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.494
• Publications: 48 publications found

Genes affected

SF3B1 (HGNC:10768): (splicing factor 3b subunit 1) This gene encodes subunit 1 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. The carboxy-terminal two-thirds of subunit 1 have 22 non-identical, tandem HEAT repeats that form rod-like, helical structures. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-197400802-A-G is Benign according to our data. Variant chr2-197400802-A-G is described in ClinVar as Benign. ClinVar VariationId is 1228123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.494 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B1	NM_012433.4	MANE Select	c.2631T>C	p.Gly877Gly	synonymous	Exon 18 of 25	NP_036565.2	O75533-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B1	ENST00000335508.11	TSL:1 MANE Select	c.2631T>C	p.Gly877Gly	synonymous	Exon 18 of 25	ENSP00000335321.6	O75533-1
	SF3B1	ENST00000929354.1		c.2628T>C	p.Gly876Gly	synonymous	Exon 18 of 25	ENSP00000599413.1
	SF3B1	ENST00000929356.1		c.2550T>C	p.Gly850Gly	synonymous	Exon 18 of 25	ENSP00000599415.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107688 AN: 151906 Hom.: 38887 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.726

GnomAD2 exomes AF: 0.658 AC: 165154 AN: 251076 AF XY: 0.669

Gnomad AFR exome AF: 0.838

Gnomad AMR exome AF: 0.495

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.526

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.681

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.676 AC: 986349 AN: 1459502 Hom.: 336277 Cov.: 35 AF XY: 0.679 AC XY: 493158 AN XY: 726262

African (AFR) AF: 0.845 AC: 28264 AN: 33442

American (AMR) AF: 0.517 AC: 23138 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 19484 AN: 26122

East Asian (EAS) AF: 0.631 AC: 25002 AN: 39644

South Asian (SAS) AF: 0.755 AC: 65120 AN: 86202

European-Finnish (FIN) AF: 0.579 AC: 30867 AN: 53282

Middle Eastern (MID) AF: 0.856 AC: 4927 AN: 5758

European-Non Finnish (NFE) AF: 0.674 AC: 748214 AN: 1110032

Other (OTH) AF: 0.685 AC: 41333 AN: 60308

GnomAD4 genome AF: 0.709 AC: 107780 AN: 152024 Hom.: 38925 Cov.: 31 AF XY: 0.706 AC XY: 52437 AN XY: 74294

African (AFR) AF: 0.834 AC: 34623 AN: 41510

American (AMR) AF: 0.649 AC: 9889 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2590 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2838 AN: 5172

South Asian (SAS) AF: 0.747 AC: 3601 AN: 4820

European-Finnish (FIN) AF: 0.571 AC: 6010 AN: 10522

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45792 AN: 67966

Other (OTH) AF: 0.725 AC: 1532 AN: 2112

Alfa AF: 0.694 Hom.: 29819

Bravo AF: 0.716

Asia WGS AF: 0.652 AC: 2269 AN: 3478

EpiCase AF: 0.708

EpiControl AF: 0.709

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SF3B1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.9
DANN	Benign	0.77
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=79/21	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: rs788018; hg19: chr2-198265526; COSMIC: COSV59206309; COSMIC: COSV59206309;