rs4894661

Variant names:

• chr3-174253925-T-C
• rs4894661
• NM_001365925.2:c.707-21390T>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.707-21390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,042 control chromosomes in the GnomAD database, including 3,748 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 0.21 (3748 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 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.707-21390T>C		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.707-21390T>C		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-21390T>C		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.707-21390T>C		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.767-21390T>C		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.647-21390T>C		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32557 AN: 151924 Hom.: 3752 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.214 AC: 32560 AN: 152042 Hom.: 3748 Cov.: 32 AF XY: 0.215 AC XY: 15987 AN XY: 74300

African (AFR) AF: 0.153 AC: 6353 AN: 41486

American (AMR) AF: 0.270 AC: 4132 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2547 AN: 5162

South Asian (SAS) AF: 0.161 AC: 777 AN: 4820

European-Finnish (FIN) AF: 0.205 AC: 2160 AN: 10544

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14947 AN: 67976

Other (OTH) AF: 0.225 AC: 474 AN: 2104

Alfa AF: 0.221 Hom.: 16225

Bravo AF: 0.220

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.54
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: rs4894661; hg19: chr3-173971715;