chr3-173479922-A-C

Variant names:

• chr3-173479922-A-C
• rs483487
• NM_001365925.2:c.-321+81859A>C

Variant summary

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

The NM_001365925.2(NLGN1):​c.-321+81859A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,012 control chromosomes in the GnomAD database, including 46,401 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 0.77 (46401 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-321+81859A>C		intron_variant	Intron 1 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.-321+81859A>C		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000457714.5	c.-321+44844A>C		intron_variant	Intron 2 of 6	1		ENSP00000392500.1
NLGN1	ENST00000423427.1	c.-321+83227A>C		intron_variant	Intron 1 of 1	4		ENSP00000407255.1
NLGN1	ENST00000413821.1	c.-321+81859A>C		intron_variant	Intron 1 of 1	4		ENSP00000401843.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116283 AN: 151894 Hom.: 46367 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.765 AC: 116363 AN: 152012 Hom.: 46401 Cov.: 31 AF XY: 0.772 AC XY: 57343 AN XY: 74312

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.777

Alfa AF: 0.810 Hom.: 10528

Bravo AF: 0.752

Asia WGS AF: 0.910 AC: 3163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs483487; hg19: chr3-173197712;