3-173947887-T-G

Variant names:

• chr3-173947887-T-G
• rs13067869
• NM_001365925.2:c.706+140055T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.706+140055T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,272 control chromosomes in the GnomAD database, including 356 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 0.058 (356 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	NM_001365925.2	MANE Select	c.706+140055T>G		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.706+140055T>G		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.706+140055T>G		intron	N/A	NP_001352853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.706+140055T>G		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.766+140055T>G		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.646+140055T>G		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8823 AN: 152154 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0579 AC: 8814 AN: 152272 Hom.: 356 Cov.: 32 AF XY: 0.0587 AC XY: 4368 AN XY: 74450

African (AFR) AF: 0.0129 AC: 536 AN: 41582

American (AMR) AF: 0.0351 AC: 536 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.146 AC: 755 AN: 5174

South Asian (SAS) AF: 0.105 AC: 508 AN: 4822

European-Finnish (FIN) AF: 0.0901 AC: 956 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5181 AN: 68004

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0686 Hom.: 807

Bravo AF: 0.0515

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.52
PhyloP100		-0.35
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: rs13067869; hg19: chr3-173665677;