rs204732

Variant names:

• chr21-31720530-G-A
• rs204732
• NM_020706.2:c.30+11133C>T

Variant summary

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

The NM_020706.2(SCAF4):​c.30+11133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,224 control chromosomes in the GnomAD database, including 1,105 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 0.11 (1105 hom., cov: 32)
• Consequence: SCAF4 NM_020706.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 4 publications found

Genes affected

SCAF4 (HGNC:19304): (SR-related CTD associated factor 4) This gene likely encodes a member of the arginine/serine-rich splicing factor family. A similar protein in Rat appears to bind the large subunit of RNA polymerase II and provide a link between transcription and pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

SCAF4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Franklin by Genoox, Ambry Genetics
• Fliedner-Zweier syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020706.2. 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
	SCAF4	NM_020706.2	MANE Select	c.30+11133C>T		intron	N/A	NP_065757.1	O95104-1
	SCAF4	NM_001145444.1		c.30+11133C>T		intron	N/A	NP_001138916.1	O95104-3
	SCAF4	NM_001145445.1		c.30+11133C>T		intron	N/A	NP_001138917.1	O95104-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAF4	ENST00000286835.12	TSL:1 MANE Select	c.30+11133C>T		intron	N/A	ENSP00000286835.7	O95104-1
	SCAF4	ENST00000434667.3	TSL:1	c.30+11133C>T		intron	N/A	ENSP00000402377.2	O95104-3
	SCAF4	ENST00000399804.5	TSL:1	c.30+11133C>T		intron	N/A	ENSP00000382703.1	O95104-2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16532 AN: 152106 Hom.: 1104 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.109 AC: 16536 AN: 152224 Hom.: 1105 Cov.: 32 AF XY: 0.105 AC XY: 7837 AN XY: 74418

African (AFR) AF: 0.0472 AC: 1959 AN: 41536

American (AMR) AF: 0.110 AC: 1677 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5188

South Asian (SAS) AF: 0.117 AC: 565 AN: 4822

European-Finnish (FIN) AF: 0.0920 AC: 976 AN: 10604

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10436 AN: 68006

Other (OTH) AF: 0.135 AC: 285 AN: 2114

Alfa AF: 0.136 Hom.: 3232

Bravo AF: 0.106

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.77
PhyloP100		0.24
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs204732;

hg19: chr21-33092843;