rs4894661

chr3-174253925-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.707-21390T>C		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-21390T>C		intron_variant			NM_001365925.2	A1

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.225

Alfa AF: 0.223 Hom.: 7900

Bravo AF: 0.220

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.3
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs4894661; hg19: chr3-173971715;