NM_001365925.2:c.707-139321G>A

Variant names:

• chr3-174135994-G-A
• rs6445141
• NM_001365925.2:c.707-139321G>A

Variant summary

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

The NM_001365925.2(NLGN1):​c.707-139321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,856 control chromosomes in the GnomAD database, including 3,306 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 0.20 (3306 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 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.707-139321G>A		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.707-139321G>A		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-139321G>A		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.707-139321G>A		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.767-139321G>A		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.647-139321G>A		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29985 AN: 151738 Hom.: 3308 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.198 AC: 30014 AN: 151856 Hom.: 3306 Cov.: 32 AF XY: 0.199 AC XY: 14761 AN XY: 74230

African (AFR) AF: 0.300 AC: 12445 AN: 41424

American (AMR) AF: 0.127 AC: 1934 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3468

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5160

South Asian (SAS) AF: 0.161 AC: 777 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2313 AN: 10536

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10170 AN: 67888

Other (OTH) AF: 0.182 AC: 384 AN: 2114

Alfa AF: 0.160 Hom.: 3507

Bravo AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.49
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: rs6445141; hg19: chr3-173853784;