rs11709498

chr3-173462843-A-Cchr3-173462843-A-T

Variant summary

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

The NM_001365925.2(NLGN1):c.-321+64780A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,128 control chromosomes in the GnomAD database, including 25,196 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 0.54 (25196 hom., cov: 33)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.-321+64780A>C		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.-321+64780A>C		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000457714.5	c.-321+27765A>C		intron_variant		1		P2
NLGN1	ENST00000413821.1	c.-321+64780A>C		intron_variant		4
NLGN1	ENST00000423427.1	c.-321+66148A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81946 AN: 152010 Hom.: 25194 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.539 AC: 81958 AN: 152128 Hom.: 25196 Cov.: 33 AF XY: 0.549 AC XY: 40803 AN XY: 74374

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.528

Alfa AF: 0.614 Hom.: 39317

Bravo AF: 0.516

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs11709498; hg19: chr3-173180633;