rs10781505

chr9-136376903-T-C

Variant summary

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

The NM_003086.4(SNAPC4):c.4285-422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,094 control chromosomes in the GnomAD database, including 13,447 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 0.42 (13447 hom., cov: 33)
• Consequence: SNAPC4 NM_003086.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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 = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAPC4	NM_003086.4	c.4285-422A>G		intron_variant		ENST00000684778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAPC4	ENST00000684778.1	c.4285-422A>G		intron_variant			NM_003086.4	P1
SNAPC4	ENST00000298532.2	c.4285-422A>G		intron_variant		1		P1
SNAPC4	ENST00000637388.2	c.4285-422A>G		intron_variant		5		P1
SNAPC4	ENST00000689006.1	c.*3498-422A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63223 AN: 151976 Hom.: 13426 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.416 AC: 63299 AN: 152094 Hom.: 13447 Cov.: 33 AF XY: 0.414 AC XY: 30814 AN XY: 74348

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.416

Alfa AF: 0.446 Hom.: 2815

Bravo AF: 0.420

Asia WGS AF: 0.396 AC: 1378 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	0.82
Dann	Benign	0.49

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: rs10781505; hg19: chr9-139271355; COSMIC: COSV53731763; COSMIC: COSV53731763;