rs912108

Positions:

• chr20-1291761-G-A
• chr20-1291761-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNPH	NM_001318234.2	c.-492-3190G>A		intron_variant		ENST00000381867.6	NP_001305163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNPH	ENST00000381867.6	c.-492-3190G>A		intron_variant		1	NM_001318234.2	ENSP00000371291.1
SNPH	ENST00000381873.7	c.-47-4564G>A		intron_variant		1		ENSP00000371297.3
SNPH	ENST00000649598.1	c.-47-4564G>A		intron_variant				ENSP00000496966.1
RAD21L1	ENST00000402452.5	c.1494-4564G>A		intron_variant		5		ENSP00000385925.1

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.265

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	17
DANN	Benign	0.74

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: rs912108; hg19: chr20-1272405;