rs1352416

Variant names:

• chr3-173762917-G-C
• rs1352416
• NM_001365925.2:c.554-44763G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.554-44763G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 151,130 control chromosomes in the GnomAD database, including 49,937 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 0.81 (49937 hom., cov: 27)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664
• Publications: 5 publications found

Genes affected

NLGN1 (HGNC:14291): (neuroligin 1) This gene encodes a member of a family of neuronal cell surface proteins. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses. [provided by RefSeq, Jul 2008]

NLGN1 Gene-Disease associations (from GenCC):

• autism, susceptibility to, 20

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. 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
	NLGN1	NM_001365925.2	MANE Select	c.554-44763G>C		intron	N/A	NP_001352854.1	A0A8Q3SHM6
	NLGN1	NM_001365923.2		c.494-37376G>C		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.554-44763G>C		intron	N/A	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.554-44763G>C		intron	N/A	ENSP00000511841.1	A0A8Q3SHM6
	NLGN1	ENST00000415045.2	TSL:1	c.554-37376G>C		intron	N/A	ENSP00000410374.2	C9J4D3
	NLGN1	ENST00000361589.8	TSL:1	c.494-44763G>C		intron	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 121949 AN: 151012 Hom.: 49898 Cov.: 27

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.808 AC: 122044 AN: 151130 Hom.: 49937 Cov.: 27 AF XY: 0.803 AC XY: 59243 AN XY: 73794

African (AFR) AF: 0.862 AC: 35496 AN: 41170

American (AMR) AF: 0.741 AC: 11182 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2656 AN: 3462

East Asian (EAS) AF: 0.429 AC: 2166 AN: 5048

South Asian (SAS) AF: 0.563 AC: 2690 AN: 4780

European-Finnish (FIN) AF: 0.891 AC: 9319 AN: 10464

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.825 AC: 55968 AN: 67812

Other (OTH) AF: 0.774 AC: 1620 AN: 2094

Alfa AF: 0.819 Hom.: 6343

Bravo AF: 0.803

Asia WGS AF: 0.531 AC: 1848 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.57
PhyloP100		-0.66
Mutation Taster		=100/0	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: rs1352416; hg19: chr3-173480707;