rs16857540

Positions:

• chr3-174182785-C-G
• chr3-174182785-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.707-92530C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,052 control chromosomes in the GnomAD database, including 4,285 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 0.22 (4285 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.707-92530C>G		intron_variant		ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-92530C>G		intron_variant			NM_001365925.2	ENSP00000511841	A1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32941 AN: 151932 Hom.: 4277 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.217 AC: 32985 AN: 152052 Hom.: 4285 Cov.: 31 AF XY: 0.213 AC XY: 15823 AN XY: 74342

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.00464

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.206

Alfa AF: 0.0890 Hom.: 103

Bravo AF: 0.231

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.39

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: rs16857540; hg19: chr3-173900575;