rs1488545

Positions:

• chr3-173765644-C-A
• chr3-173765644-C-G

Variant summary

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

The NM_001365925.2(NLGN1):​c.554-42036C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,096 control chromosomes in the GnomAD database, including 48,663 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 0.79 (48663 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.554-42036C>A		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.554-42036C>A		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8	c.494-42036C>A		intron_variant		1		P2
NLGN1	ENST00000415045.2	c.554-34649C>A		intron_variant		1
NLGN1	ENST00000457714.5	c.494-42036C>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120714 AN: 151978 Hom.: 48633 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.794 AC: 120799 AN: 152096 Hom.: 48663 Cov.: 31 AF XY: 0.789 AC XY: 58679 AN XY: 74358

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.766

Alfa AF: 0.791 Hom.: 20311

Bravo AF: 0.789

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.024
DANN	Benign	0.19

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: rs1488545; hg19: chr3-173483434;