rs6445137

chr3-174057494-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.707-217821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,018 control chromosomes in the GnomAD database, including 1,827 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 0.15 (1827 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.707-217821C>T		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-217821C>T		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8	c.647-217821C>T		intron_variant		1		P2
NLGN1	ENST00000415045.2	c.767-217821C>T		intron_variant		1
NLGN1	ENST00000457714.5	c.647-217821C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23114 AN: 151886 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.152 AC: 23121 AN: 152004 Hom.: 1827 Cov.: 32 AF XY: 0.150 AC XY: 11135 AN XY: 74320

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.0950

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.147

Alfa AF: 0.154 Hom.: 924

Bravo AF: 0.148

Asia WGS AF: 0.116 AC: 404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.9
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: rs6445137; hg19: chr3-173775284;