rs1045881

Variant names:

• chr2-49921834-C-T
• rs1045881
• NM_001330078.2:c.*110G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-49921834-C-T
• chr2-49921834-C-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001330078.2(NRXN1):​c.*110G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.165 in 1,054,496 control chromosomes in the GnomAD database, including 15,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1882 hom., cov: 32)
  • Exomes 𝑓: 0.17 (13859 hom.)
• Consequence: NRXN1 NM_001330078.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.22
• Publications: 22 publications found

Genes affected

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]

NRXN1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• chromosome 2p16.3 deletion syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Pitt-Hopkins-like syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autism

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 2-49921834-C-T is Benign according to our data. Variant chr2-49921834-C-T is described in ClinVar as Benign. ClinVar VariationId is 336539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330078.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN1	NM_001330078.2	MANE Select	c.*110G>A		3_prime_UTR	Exon 23 of 23	NP_001317007.1	Q9ULB1-5
	NRXN1	NM_001135659.3		c.*110G>A		3_prime_UTR	Exon 24 of 24	NP_001129131.1	Q9ULB1-3
	NRXN1	NM_001330093.2		c.*110G>A		3_prime_UTR	Exon 23 of 23	NP_001317022.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRXN1	ENST00000401669.7	TSL:5 MANE Select	c.*110G>A		3_prime_UTR	Exon 23 of 23	ENSP00000385017.2	Q9ULB1-5
	NRXN1	ENST00000404971.5	TSL:1	c.*110G>A		3_prime_UTR	Exon 24 of 24	ENSP00000385142.1	Q9ULB1-3
	NRXN1	ENST00000625672.2	TSL:1	c.*110G>A		3_prime_UTR	Exon 21 of 21	ENSP00000485887.1	Q9ULB1-2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23223 AN: 151810 Hom.: 1883 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.167 AC: 150826 AN: 902568 Hom.: 13859 Cov.: 12 AF XY: 0.173 AC XY: 79274 AN XY: 458056

African (AFR) AF: 0.128 AC: 2644 AN: 20694

American (AMR) AF: 0.0915 AC: 2284 AN: 24954

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 3052 AN: 18724

East Asian (EAS) AF: 0.135 AC: 4613 AN: 34278

South Asian (SAS) AF: 0.313 AC: 18292 AN: 58352

European-Finnish (FIN) AF: 0.149 AC: 6662 AN: 44846

Middle Eastern (MID) AF: 0.233 AC: 726 AN: 3116

European-Non Finnish (NFE) AF: 0.161 AC: 105661 AN: 657212

Other (OTH) AF: 0.171 AC: 6892 AN: 40392

GnomAD4 genome AF: 0.153 AC: 23224 AN: 151928 Hom.: 1882 Cov.: 32 AF XY: 0.155 AC XY: 11477 AN XY: 74268

African (AFR) AF: 0.131 AC: 5420 AN: 41424

American (AMR) AF: 0.117 AC: 1783 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3468

East Asian (EAS) AF: 0.144 AC: 745 AN: 5186

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4814

European-Finnish (FIN) AF: 0.161 AC: 1692 AN: 10538

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10929 AN: 67940

Other (OTH) AF: 0.156 AC: 328 AN: 2104

Alfa AF: 0.162 Hom.: 8442

Bravo AF: 0.146

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Pitt-Hopkins-like syndrome 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		4.2
Mutation Taster		=98/2	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: rs1045881; hg19: chr2-50148972; COSMIC: COSV60489450; COSMIC: COSV60489450;