rs16828127

chr3-173600062-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.-320-4217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,076 control chromosomes in the GnomAD database, including 786 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 0.094 (786 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.-320-4217T>C		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.-320-4217T>C		intron_variant			NM_001365925.2	A1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14312 AN: 151956 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0941 AC: 14314 AN: 152076 Hom.: 786 Cov.: 32 AF XY: 0.0997 AC XY: 7412 AN XY: 74350

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0912

Gnomad4 OTH AF: 0.101

Alfa AF: 0.100 Hom.: 1091

Bravo AF: 0.0903

Asia WGS AF: 0.171 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.5
Dann	Benign	0.85

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: rs16828127; hg19: chr3-173317852;