NM_001365925.2:c.707-92530C>G

Variant names:

• chr3-174182785-C-G
• rs16857540
• NM_001365925.2:c.707-92530C>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.707-92530C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,052 control chromosomes in the GnomAD database, including 4,285 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 0.22 (4285 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 7 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

ENSG00000302290 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 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.707-92530C>G		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.707-92530C>G		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-92530C>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.707-92530C>G		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.767-92530C>G		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.647-92530C>G		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32941 AN: 151932 Hom.: 4277 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.217 AC: 32985 AN: 152052 Hom.: 4285 Cov.: 31 AF XY: 0.213 AC XY: 15823 AN XY: 74342

African (AFR) AF: 0.356 AC: 14757 AN: 41436

American (AMR) AF: 0.218 AC: 3328 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5174

South Asian (SAS) AF: 0.197 AC: 949 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1108 AN: 10600

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11326 AN: 67966

Other (OTH) AF: 0.206 AC: 433 AN: 2106

Alfa AF: 0.0890 Hom.: 103

Bravo AF: 0.231

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.39
PhyloP100		-1.3
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: rs16857540; hg19: chr3-173900575;