NM_001365925.2:c.-321+64780A>C

Variant names:

• chr3-173462843-A-C
• rs11709498
• NM_001365925.2:c.-321+64780A>C

Variant summary

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

The NM_001365925.2(NLGN1):​c.-321+64780A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,128 control chromosomes in the GnomAD database, including 25,196 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 0.54 (25196 hom., cov: 33)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	NM_001365925.2	MANE Select	c.-321+64780A>C		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.-321+66148A>C		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.-321+66148A>C		intron	N/A	NP_001352853.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.-321+64780A>C		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000457714.5	TSL:1	c.-321+27765A>C		intron	N/A	ENSP00000392500.1
	NLGN1	ENST00000423427.1	TSL:4	c.-321+66148A>C		intron	N/A	ENSP00000407255.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81946 AN: 152010 Hom.: 25194 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.539 AC: 81958 AN: 152128 Hom.: 25196 Cov.: 33 AF XY: 0.549 AC XY: 40803 AN XY: 74374

African (AFR) AF: 0.230 AC: 9547 AN: 41504

American (AMR) AF: 0.631 AC: 9637 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1871 AN: 3470

East Asian (EAS) AF: 0.903 AC: 4682 AN: 5184

South Asian (SAS) AF: 0.677 AC: 3263 AN: 4820

European-Finnish (FIN) AF: 0.734 AC: 7774 AN: 10588

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43322 AN: 67976

Other (OTH) AF: 0.528 AC: 1118 AN: 2116

Alfa AF: 0.598 Hom.: 85897

Bravo AF: 0.516

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11709498; hg19: chr3-173180633;