rs17713068

chr19-40764150-T-G

Variant summary

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

The NM_004596.5(SNRPA):c.689+475T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,016 control chromosomes in the GnomAD database, including 1,285 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 0.12 (1285 hom., cov: 32)
• Consequence: SNRPA NM_004596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57

Genes affected

SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRPA	NM_004596.5	c.689+475T>G		intron_variant		ENST00000243563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRPA	ENST00000243563.8	c.689+475T>G		intron_variant		1	NM_004596.5	P1
SNRPA	ENST00000601393.1	c.626+475T>G		intron_variant		3
SNRPA	ENST00000601545.5	c.539+475T>G		intron_variant		5
SNRPA	ENST00000596860.1	n.135+475T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18374 AN: 151898 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.121 AC: 18398 AN: 152016 Hom.: 1285 Cov.: 32 AF XY: 0.122 AC XY: 9078 AN XY: 74328

Gnomad4 AFR AF: 0.0707

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0797

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.114

Alfa AF: 0.145 Hom.: 354

Bravo AF: 0.115

Asia WGS AF: 0.125 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.61
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: rs17713068; hg19: chr19-41270055;