rs11794847

Positions:

• chr9-136377295-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAPC4	NM_003086.4	c.4284+248C>T		intron_variant		ENST00000684778.1	NP_003077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAPC4	ENST00000684778.1	c.4284+248C>T		intron_variant			NM_003086.4	ENSP00000510559	P1
SNAPC4	ENST00000298532.2	c.4284+248C>T		intron_variant		1		ENSP00000298532	P1
SNAPC4	ENST00000637388.2	c.4284+248C>T		intron_variant		5		ENSP00000490037	P1
SNAPC4	ENST00000689006.1	c.*3497+248C>T		intron_variant, NMD_transcript_variant				ENSP00000509362

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.353

Alfa AF: 0.402 Hom.: 2060

Bravo AF: 0.375

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs11794847; hg19: chr9-139271747; COSMIC: COSV53731475; COSMIC: COSV53731475;