3-173471483-T-C

Variant names:

• chr3-173471483-T-C
• rs721729
• NM_001365925.2:c.-321+73420T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.-321+73420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,964 control chromosomes in the GnomAD database, including 20,845 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 0.50 (20845 hom., cov: 31)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 6 publications found

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]

NLGN1 Gene-Disease associations (from GenCC):

• autism, susceptibility to, 20

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-321+73420T>C		intron_variant	Intron 1 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.-321+73420T>C		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000457714.5	c.-321+36405T>C		intron_variant	Intron 2 of 6	1		ENSP00000392500.1
NLGN1	ENST00000423427.1	c.-321+74788T>C		intron_variant	Intron 1 of 1	4		ENSP00000407255.1
NLGN1	ENST00000413821.1	c.-321+73420T>C		intron_variant	Intron 1 of 1	4		ENSP00000401843.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75436 AN: 151846 Hom.: 20840 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.497 AC: 75469 AN: 151964 Hom.: 20845 Cov.: 31 AF XY: 0.506 AC XY: 37584 AN XY: 74258

African (AFR) AF: 0.250 AC: 10374 AN: 41468

American (AMR) AF: 0.606 AC: 9230 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3468

East Asian (EAS) AF: 0.842 AC: 4343 AN: 5156

South Asian (SAS) AF: 0.552 AC: 2657 AN: 4812

European-Finnish (FIN) AF: 0.668 AC: 7057 AN: 10560

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38760 AN: 67944

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.499 Hom.: 4593

Bravo AF: 0.481

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.48
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs721729; hg19: chr3-173189273;