2-51036011-A-G

Position:

• chr2-51036011-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_135237.1(LOC730100):​n.416+2995A>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 0.602 in 151,894 control chromosomes in the GnomAD database, including 27,827 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 0.60 (27827 hom., cov: 31)
• Consequence: LOC730100 NR_135237.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC730100	NR_135237.1	n.416+2995A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000440698.1	n.416+2995A>G		intron_variant, non_coding_transcript_variant		2
NRXN1	ENST00000635126.1	n.320-2877T>C		intron_variant, non_coding_transcript_variant		5
NRXN1	ENST00000635310.1	n.426-6817T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91346 AN: 151776 Hom.: 27790 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.602 AC: 91440 AN: 151894 Hom.: 27827 Cov.: 31 AF XY: 0.601 AC XY: 44569 AN XY: 74214

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.564

Alfa AF: 0.560 Hom.: 11049

Bravo AF: 0.601

Asia WGS AF: 0.617 AC: 2141 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1995584; hg19: chr2-51263149;