3-173767581-C-T

Position:

• chr3-173767581-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.554-40099C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,726 control chromosomes in the GnomAD database, including 30,368 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 0.61 (30368 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.554-40099C>T		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.554-40099C>T		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000361589.8	c.494-40099C>T		intron_variant		1		P2
NLGN1	ENST00000415045.2	c.554-32712C>T		intron_variant		1
NLGN1	ENST00000457714.5	c.494-40099C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93269 AN: 151610 Hom.: 30368 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.615 AC: 93291 AN: 151726 Hom.: 30368 Cov.: 32 AF XY: 0.614 AC XY: 45574 AN XY: 74176

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.601

Alfa AF: 0.699 Hom.: 52519

Bravo AF: 0.599

Asia WGS AF: 0.412 AC: 1427 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.63

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: rs976683; hg19: chr3-173485371;