rs11145797

Positions:

• chr9-136380580-G-A
• chr9-136380580-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003086.4(SNAPC4):​c.2499+160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,180 control chromosomes in the GnomAD database, including 1,764 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 0.15 (1764 hom., cov: 33)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.2499+160C>T		intron_variant		ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.2499+160C>T		intron_variant			NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.2499+160C>T		intron_variant		1		P1
SNAPC4	ENST00000637388.2	c.2499+160C>T		intron_variant		5		P1
SNAPC4	ENST00000689006.1	c.*1712+160C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22517 AN: 152062 Hom.: 1753 Cov.: 33

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.148 AC: 22559 AN: 152180 Hom.: 1764 Cov.: 33 AF XY: 0.147 AC XY: 10959 AN XY: 74392

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.130

Alfa AF: 0.161 Hom.: 261

Bravo AF: 0.151

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.69

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: rs11145797; hg19: chr9-139275032; COSMIC: COSV53738979; COSMIC: COSV53738979;