2-51044980-A-G

Position:

• chr2-51044980-A-G

Variant summary

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

The NR_135237.1(LOC730100):​n.417-7377A>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 0.0999 in 152,256 control chromosomes in the GnomAD database, including 851 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 0.10 (851 hom., cov: 33)
• Consequence: LOC730100 NR_135237.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC730100	NR_135237.1	n.417-7377A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000440698.1	n.417-7377A>G		intron_variant, non_coding_transcript_variant		2
NRXN1	ENST00000635126.1	n.320-11846T>C		intron_variant, non_coding_transcript_variant		5
NRXN1	ENST00000635310.1	n.426-15786T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15181 AN: 152138 Hom.: 846 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.0999 AC: 15207 AN: 152256 Hom.: 851 Cov.: 33 AF XY: 0.101 AC XY: 7496 AN XY: 74444

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0714

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0903 Hom.: 123

Bravo AF: 0.0998

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11889082; hg19: chr2-51272118;