chr3-174193024-T-A

Position:

• chr3-174193024-T-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.707-82291T>A		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-82291T>A		intron_variant			NM_001365925.2	A1

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

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.539

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.57

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: rs6806890; hg19: chr3-173910814;