rs12626622

Variant names:

• chr21-31687276-C-T
• rs12626622
• NM_020706.2:c.2043+1031G>A

Variant summary

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

The NM_020706.2(SCAF4):​c.2043+1031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,030 control chromosomes in the GnomAD database, including 5,607 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 0.23 (5607 hom., cov: 32)
• Consequence: SCAF4 NM_020706.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• 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: Franklin by Genoox, Ambry Genetics, ClinGen
• Fliedner-Zweier syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 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.2043+1031G>A		intron	N/A	NP_065757.1	O95104-1
	SCAF4	NM_001145444.1		c.1998+1031G>A		intron	N/A	NP_001138916.1	O95104-3
	SCAF4	NM_001145445.1		c.2043+1031G>A		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.2043+1031G>A		intron	N/A	ENSP00000286835.7	O95104-1
	SCAF4	ENST00000434667.3	TSL:1	c.1998+1031G>A		intron	N/A	ENSP00000402377.2	O95104-3
	SCAF4	ENST00000399804.5	TSL:1	c.2043+1031G>A		intron	N/A	ENSP00000382703.1	O95104-2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34639 AN: 151912 Hom.: 5584 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.228 AC: 34714 AN: 152030 Hom.: 5607 Cov.: 32 AF XY: 0.232 AC XY: 17205 AN XY: 74314

African (AFR) AF: 0.420 AC: 17418 AN: 41452

American (AMR) AF: 0.248 AC: 3786 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.509 AC: 2629 AN: 5168

South Asian (SAS) AF: 0.222 AC: 1067 AN: 4816

European-Finnish (FIN) AF: 0.191 AC: 2014 AN: 10570

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7020 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2108

Alfa AF: 0.146 Hom.: 1322

Bravo AF: 0.245

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs12626622; hg19: chr21-33059589;