rs9290474

Variant names:

• chr3-173553894-C-A
• rs9290474
• NM_001365925.2:c.-320-50385C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-173553894-C-A
• chr3-173553894-C-G
• chr3-173553894-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-320-50385C>A		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.-320-50385C>A		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000457714.5	c.-320-50385C>A		intron_variant	Intron 2 of 6	1		ENSP00000392500.1
NLGN1	ENST00000423427.1	c.-320-50385C>A		intron_variant	Intron 1 of 1	4		ENSP00000407255.1
NLGN1	ENST00000413821.1	c.-320-50385C>A		intron_variant	Intron 1 of 1	4		ENSP00000401843.1

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

African (AFR) AF: 0.654 AC: 27109 AN: 41466

American (AMR) AF: 0.547 AC: 8337 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3466

East Asian (EAS) AF: 0.803 AC: 4135 AN: 5152

South Asian (SAS) AF: 0.624 AC: 3008 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5740 AN: 10526

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33944 AN: 67880

Other (OTH) AF: 0.531 AC: 1118 AN: 2106

Alfa AF: 0.492 Hom.: 7577

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
PhyloP100		-0.13
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: rs9290474; hg19: chr3-173271684;