rs11794847

Variant names:

• chr9-136377295-G-A
• rs11794847
• NM_003086.4:c.4284+248C>T

Variant summary

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

The NM_003086.4(SNAPC4):​c.4284+248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,150 control chromosomes in the GnomAD database, including 11,285 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 0.38 (11285 hom., cov: 34)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 19 publications found

Genes affected

SNAPC4 (HGNC:11137): (small nuclear RNA activating complex polypeptide 4) This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis. [provided by RefSeq, Jul 2016]

SNAPC4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Baylor College of Medicine Research Center, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003086.4. 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
	SNAPC4	NM_003086.4	MANE Select	c.4284+248C>T		intron	N/A	NP_003077.2	Q5SXM2
	SNAPC4	NM_001394201.1		c.4284+248C>T		intron	N/A	NP_001381130.1	Q5SXM2
	SNAPC4	NM_001394202.1		c.4200+248C>T		intron	N/A	NP_001381131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAPC4	ENST00000684778.1	MANE Select	c.4284+248C>T		intron	N/A	ENSP00000510559.1	Q5SXM2
	SNAPC4	ENST00000298532.2	TSL:1	c.4284+248C>T		intron	N/A	ENSP00000298532.2	Q5SXM2
	SNAPC4	ENST00000637388.2	TSL:5	c.4284+248C>T		intron	N/A	ENSP00000490037.2	Q5SXM2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57437 AN: 152032 Hom.: 11268 Cov.: 34

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.378 AC: 57504 AN: 152150 Hom.: 11285 Cov.: 34 AF XY: 0.376 AC XY: 27988 AN XY: 74368

African (AFR) AF: 0.287 AC: 11924 AN: 41508

American (AMR) AF: 0.472 AC: 7222 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5166

South Asian (SAS) AF: 0.328 AC: 1585 AN: 4826

European-Finnish (FIN) AF: 0.413 AC: 4370 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28430 AN: 67976

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.370 Hom.: 4484

Bravo AF: 0.375

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.44
PhyloP100		-2.3
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: rs11794847; hg19: chr9-139271747; COSMIC: COSV53731475; COSMIC: COSV53731475;