1-149923683-T-A

Variant names:

• chr1-149923683-T-A
• rs1390654592
• NM_005850.5:c.1134A>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005850.5(SF3B4):​c.1134A>T​(p.Pro378Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 1,525,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SF3B4 NM_005850.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 0 publications found

Genes affected

SF3B4 (HGNC:10771): (splicing factor 3b subunit 4) This gene encodes one of four subunits of the splicing factor 3B. The protein encoded by this gene cross-links to a region in the pre-mRNA immediately upstream of the branchpoint sequence in pre-mRNA in the prespliceosomal complex A. It also may be involved in the assembly of the B, C and E spliceosomal complexes. In addition to RNA-binding activity, this protein interacts directly and highly specifically with subunit 2 of the splicing factor 3B. This protein contains two N-terminal RNA-recognition motifs (RRMs), consistent with the observation that it binds directly to pre-mRNA. [provided by RefSeq, Jul 2008]

SF3B4 Gene-Disease associations (from GenCC):

• Nager acrofacial dysostosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• SF3B4-related acrofacial dysostosis

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• acrofacial dysostosis Rodriguez type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-149923683-T-A is Benign according to our data. Variant chr1-149923683-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2895785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005850.5. 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
	SF3B4	NM_005850.5	MANE Select	c.1134A>T	p.Pro378Pro	synonymous	Exon 6 of 6	NP_005841.1	Q15427

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B4	ENST00000271628.9	TSL:1 MANE Select	c.1134A>T	p.Pro378Pro	synonymous	Exon 6 of 6	ENSP00000271628.8	Q15427
	SF3B4	ENST00000940764.1		c.825A>T	p.Pro275Pro	synonymous	Exon 6 of 6	ENSP00000610823.1
	SF3B4	ENST00000940765.1		c.663A>T	p.Pro221Pro	synonymous	Exon 6 of 6	ENSP00000610824.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000291 AC: 4 AN: 1373284 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 680440

African (AFR) AF: 0.00 AC: 0 AN: 27688

American (AMR) AF: 0.00 AC: 0 AN: 24366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21900

East Asian (EAS) AF: 0.00 AC: 0 AN: 34400

South Asian (SAS) AF: 0.00 AC: 0 AN: 71572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1079446

Other (OTH) AF: 0.0000177 AC: 1 AN: 56540

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74154

African (AFR) AF: 0.00 AC: 0 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.3
DANN	Benign	0.82
PhyloP100		-1.5
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1390654592; hg19: chr1-149895575;