NM_001365925.2:c.707-82291T>A

Variant names:

• chr3-174193024-T-A
• rs6806890
• NM_001365925.2:c.707-82291T>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.707-82291T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,812 control chromosomes in the GnomAD database, including 22,322 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 0.53 (22322 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 1 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: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000302290 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.804 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.707-82291T>A		intron	N/A	NP_001352854.1	A0A8Q3SHM6
	NLGN1	NM_001365923.2		c.707-82291T>A		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-82291T>A		intron	N/A	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.707-82291T>A		intron	N/A	ENSP00000511841.1	A0A8Q3SHM6
	NLGN1	ENST00000415045.2	TSL:1	c.767-82291T>A		intron	N/A	ENSP00000410374.2	C9J4D3
	NLGN1	ENST00000361589.8	TSL:1	c.647-82291T>A		intron	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80924 AN: 151694 Hom.: 22319 Cov.: 31

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.533 AC: 80970 AN: 151812 Hom.: 22322 Cov.: 31 AF XY: 0.535 AC XY: 39673 AN XY: 74210

African (AFR) AF: 0.421 AC: 17443 AN: 41392

American (AMR) AF: 0.557 AC: 8496 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3462

East Asian (EAS) AF: 0.825 AC: 4250 AN: 5154

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4820

European-Finnish (FIN) AF: 0.669 AC: 7031 AN: 10506

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.562 AC: 38205 AN: 67926

Other (OTH) AF: 0.539 AC: 1137 AN: 2108

Alfa AF: 0.538 Hom.: 2757

Bravo AF: 0.525

Asia WGS AF: 0.602 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		-0.072
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: rs6806890; hg19: chr3-173910814;