rs2353307

chr2-51160353-C-Gchr2-51160353-C-T

Variant summary

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

The NR_135237.1(LOC730100):n.514+107899C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,060 control chromosomes in the GnomAD database, including 2,831 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 0.18 (2831 hom., cov: 32)
• Consequence: LOC730100 NR_135237.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

(HGNC:):

NRXN1 (HGNC:8008): (neurexin 1) This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC730100	NR_135237.1	n.514+107899C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000440698.1	n.514+107899C>G		intron_variant, non_coding_transcript_variant		2
NRXN1	ENST00000635126.1	n.183+61318G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27608 AN: 151942 Hom.: 2830 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.182 AC: 27627 AN: 152060 Hom.: 2831 Cov.: 32 AF XY: 0.178 AC XY: 13263 AN XY: 74338

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.203

Alfa AF: 0.112 Hom.: 185

Bravo AF: 0.178

Asia WGS AF: 0.189 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.63
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2353307; hg19: chr2-51387491;