1-227747654-T-C

Variant summary

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

The NM_053052.4(SNAP47):c.-45-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,542,224 control chromosomes in the GnomAD database, including 281,863 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 0.68 (36615 hom., cov: 32)
  • Exomes 𝑓: 0.59 (245248 hom.)
• Consequence: SNAP47 NM_053052.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.83

Genes affected

SNAP47 (HGNC:30669): (synaptosome associated protein 47) Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -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 = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNAP47	NM_053052.4	c.-45-38T>C		intron_variant		ENST00000617596.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNAP47	ENST00000617596.5	c.-45-38T>C		intron_variant		1	NM_053052.4	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103076 AN: 151922 Hom.: 36548 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.665

GnomAD3 exomes AF: 0.637 AC: 128178 AN: 201364 Hom.: 41947 AF XY: 0.624 AC XY: 66537 AN XY: 106574

Gnomad AFR exome AF: 0.903

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.767

Gnomad SAS exome AF: 0.616

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.590 AC: 819834 AN: 1390184 Hom.: 245248 Cov.: 34 AF XY: 0.589 AC XY: 401894 AN XY: 682132

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.721

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.679 AC: 103200 AN: 152040 Hom.: 36615 Cov.: 32 AF XY: 0.678 AC XY: 50412 AN XY: 74320

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.666

Alfa AF: 0.577 Hom.: 4832

Bravo AF: 0.696

Asia WGS AF: 0.684 AC: 2378 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.14
Dann	Benign	0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2236360; hg19: chr1-227935355;