chr20-1291761-G-A

Variant names:

• chr20-1291761-G-A
• rs912108
• NM_001318234.2:c.-492-3190G>A

Variant summary

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

The NM_001318234.2(SNPH):​c.-492-3190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,100 control chromosomes in the GnomAD database, including 6,411 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 0.28 (6411 hom., cov: 33)
• Consequence: SNPH NM_001318234.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817
• Publications: 3 publications found

Genes affected

SNPH (HGNC:15931): (syntaphilin) Syntaxin-1, synaptobrevin/VAMP, and SNAP25 interact to form the SNARE complex, which is required for synaptic vesicle docking and fusion. The protein encoded by this gene is membrane-associated and inhibits SNARE complex formation by binding free syntaxin-1. Expression of this gene appears to be brain-specific. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

RAD21L1 (HGNC:16271): (RAD21 cohesin complex component like 1) Predicted to enable chromatin binding activity. Predicted to be involved in mitotic sister chromatid cohesion; replication-born double-strand break repair via sister chromatid exchange; and synaptonemal complex assembly. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; homologous chromosome segregation; and seminiferous tubule development. Predicted to be located in lateral element. Predicted to be part of nuclear meiotic cohesin complex and nuclear mitotic cohesin complex. Predicted to be active in synaptonemal 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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318234.2. 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
	SNPH	NM_001318234.2	MANE Select	c.-492-3190G>A		intron	N/A	NP_001305163.1
	SNPH	NM_001439257.1		c.-492-3190G>A		intron	N/A	NP_001426186.1
	SNPH	NM_001439258.1		c.-464-4015G>A		intron	N/A	NP_001426187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNPH	ENST00000381867.6	TSL:1 MANE Select	c.-492-3190G>A		intron	N/A	ENSP00000371291.1
	SNPH	ENST00000381873.7	TSL:1	c.-47-4564G>A		intron	N/A	ENSP00000371297.3
	SNPH	ENST00000649598.1		c.-47-4564G>A		intron	N/A	ENSP00000496966.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42554 AN: 151980 Hom.: 6420 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.280 AC: 42541 AN: 152100 Hom.: 6411 Cov.: 33 AF XY: 0.280 AC XY: 20853 AN XY: 74348

African (AFR) AF: 0.158 AC: 6539 AN: 41502

American (AMR) AF: 0.294 AC: 4490 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1810 AN: 5168

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3098 AN: 10560

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22728 AN: 67976

Other (OTH) AF: 0.265 AC: 559 AN: 2110

Alfa AF: 0.309 Hom.: 933

Bravo AF: 0.275

Asia WGS AF: 0.332 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.74
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs912108; hg19: chr20-1272405;