rs9290474

chr3-173553894-C-Achr3-173553894-C-Gchr3-173553894-C-T

Variant summary

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

The NM_001365925.2(NLGN1):c.-320-50385C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,866 control chromosomes in the GnomAD database, including 23,872 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 0.56 (23872 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.-320-50385C>A		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.-320-50385C>A		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000457714.5	c.-320-50385C>A		intron_variant		1		P2
NLGN1	ENST00000413821.1	c.-320-50385C>A		intron_variant		4
NLGN1	ENST00000423427.1	c.-320-50385C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85229 AN: 151748 Hom.: 23829 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.562 AC: 85329 AN: 151866 Hom.: 23872 Cov.: 32 AF XY: 0.569 AC XY: 42205 AN XY: 74222

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.531

Alfa AF: 0.489 Hom.: 6476

Asia WGS AF: 0.700 AC: 2433 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.9
Dann	Benign	0.73

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: rs9290474; hg19: chr3-173271684;