1-227747654-T-C

Variant names:

• chr1-227747654-T-C
• rs2236360
• NM_053052.4:c.-45-38T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

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 = 0.889 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053052.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP47	NM_053052.4	MANE Select	c.-45-38T>C		intron	N/A	NP_444280.3	A0A087X0B7
	SNAP47	NM_001323935.1		c.91-38T>C		intron	N/A	NP_001310864.1	Q5SQN1-2
	SNAP47	NM_001323930.2		c.-45-38T>C		intron	N/A	NP_001310859.1	A0A087X0B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP47	ENST00000617596.5	TSL:1 MANE Select	c.-45-38T>C		intron	N/A	ENSP00000483253.1	A0A087X0B7
	SNAP47	ENST00000366759.9	TSL:1	c.-45-38T>C		intron	N/A	ENSP00000355721.5	A0A087X0B7
	SNAP47	ENST00000315781.10	TSL:1	c.-45-38T>C		intron	N/A	ENSP00000314157.7	A0A7P0T8U4

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

GnomAD2 exomes AF: 0.637 AC: 128178 AN: 201364 AF XY: 0.624

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 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

African (AFR) AF: 0.909 AC: 28697 AN: 31572

American (AMR) AF: 0.721 AC: 26813 AN: 37208

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 12364 AN: 21704

East Asian (EAS) AF: 0.776 AC: 30224 AN: 38942

South Asian (SAS) AF: 0.619 AC: 46153 AN: 74514

European-Finnish (FIN) AF: 0.571 AC: 28977 AN: 50726

Middle Eastern (MID) AF: 0.615 AC: 3337 AN: 5426

European-Non Finnish (NFE) AF: 0.567 AC: 608224 AN: 1072868

Other (OTH) AF: 0.612 AC: 35045 AN: 57224

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

African (AFR) AF: 0.896 AC: 37185 AN: 41490

American (AMR) AF: 0.680 AC: 10393 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1998 AN: 3468

East Asian (EAS) AF: 0.767 AC: 3949 AN: 5150

South Asian (SAS) AF: 0.631 AC: 3035 AN: 4812

European-Finnish (FIN) AF: 0.572 AC: 6038 AN: 10560

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38571 AN: 67956

Other (OTH) AF: 0.666 AC: 1406 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.18
PhyloP100		-3.8
PromoterAI		0.0018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236360; hg19: chr1-227935355;