19-40761224-T-C

Variant names:

• chr19-40761224-T-C
• rs2607414
• NM_004596.5:c.426+1614T>C

Variant summary

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

The NM_004596.5(SNRPA):​c.426+1614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 151,744 control chromosomes in the GnomAD database, including 45,276 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 0.77 (45276 hom., cov: 29)
• Consequence: SNRPA NM_004596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 6 publications found

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]

SNRPA Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004596.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA	NM_004596.5	MANE Select	c.426+1614T>C		intron	N/A	NP_004587.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRPA	ENST00000243563.8	TSL:1 MANE Select	c.426+1614T>C		intron	N/A	ENSP00000243563.2
	SNRPA	ENST00000601393.1	TSL:3	c.363+1614T>C		intron	N/A	ENSP00000472355.1
	SNRPA	ENST00000601545.5	TSL:5	c.276+1614T>C		intron	N/A	ENSP00000470534.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116667 AN: 151626 Hom.: 45215 Cov.: 29

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.770 AC: 116791 AN: 151744 Hom.: 45276 Cov.: 29 AF XY: 0.770 AC XY: 57046 AN XY: 74126

African (AFR) AF: 0.841 AC: 34822 AN: 41396

American (AMR) AF: 0.778 AC: 11838 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3694 AN: 5148

South Asian (SAS) AF: 0.630 AC: 3035 AN: 4814

European-Finnish (FIN) AF: 0.810 AC: 8489 AN: 10474

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49952 AN: 67922

Other (OTH) AF: 0.746 AC: 1563 AN: 2096

Alfa AF: 0.756 Hom.: 11602

Bravo AF: 0.773

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.53
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2607414; hg19: chr19-41267129;