rs1352416

Positions:

• chr3-173762917-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.554-44763G>C		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.554-44763G>C		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8	c.494-44763G>C		intron_variant		1		P2
NLGN1	ENST00000415045.2	c.554-37376G>C		intron_variant		1
NLGN1	ENST00000457714.5	c.494-44763G>C		intron_variant		1		P2

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

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.774

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs1352416; hg19: chr3-173480707;