3-173765644-C-A

Variant names:

• chr3-173765644-C-A
• rs1488545
• NM_001365925.2:c.554-42036C>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.554-42036C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,096 control chromosomes in the GnomAD database, including 48,663 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 0.79 (48663 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 6 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 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.554-42036C>A		intron	N/A	NP_001352854.1	A0A8Q3SHM6
	NLGN1	NM_001365923.2		c.494-34649C>A		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.554-42036C>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.554-42036C>A		intron	N/A	ENSP00000511841.1	A0A8Q3SHM6
	NLGN1	ENST00000415045.2	TSL:1	c.554-34649C>A		intron	N/A	ENSP00000410374.2	C9J4D3
	NLGN1	ENST00000361589.8	TSL:1	c.494-42036C>A		intron	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120714 AN: 151978 Hom.: 48633 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.794 AC: 120799 AN: 152096 Hom.: 48663 Cov.: 31 AF XY: 0.789 AC XY: 58679 AN XY: 74358

African (AFR) AF: 0.824 AC: 34206 AN: 41500

American (AMR) AF: 0.733 AC: 11184 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2629 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2107 AN: 5156

South Asian (SAS) AF: 0.558 AC: 2686 AN: 4812

European-Finnish (FIN) AF: 0.888 AC: 9415 AN: 10602

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56007 AN: 67980

Other (OTH) AF: 0.766 AC: 1617 AN: 2112

Alfa AF: 0.794 Hom.: 22890

Bravo AF: 0.789

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.024
DANN	Benign	0.19
PhyloP100		-1.2
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: rs1488545; hg19: chr3-173483434;