3-173666799-A-C

Variant names:

• chr3-173666799-A-C
• rs11713169
• NM_001365925.2:c.553+61206A>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.553+61206A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,188 control chromosomes in the GnomAD database, including 1,137 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 0.11 (1137 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.553+61206A>C		intron_variant	Intron 3 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.553+61206A>C		intron_variant	Intron 3 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000415045.2	c.553+61206A>C		intron_variant	Intron 3 of 7	1		ENSP00000410374.2
NLGN1	ENST00000361589.8	c.493+61708A>C		intron_variant	Intron 2 of 5	1		ENSP00000354541.4
NLGN1	ENST00000457714.5	c.493+61708A>C		intron_variant	Intron 3 of 6	1		ENSP00000392500.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16375 AN: 152068 Hom.: 1137 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0907

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.108 AC: 16361 AN: 152188 Hom.: 1137 Cov.: 32 AF XY: 0.110 AC XY: 8174 AN XY: 74406

African (AFR) AF: 0.0270 AC: 1123 AN: 41554

American (AMR) AF: 0.0830 AC: 1269 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 315 AN: 3472

East Asian (EAS) AF: 0.109 AC: 564 AN: 5164

South Asian (SAS) AF: 0.112 AC: 540 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1918 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10307 AN: 67990

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.136 Hom.: 2023

Bravo AF: 0.0971

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.48
PhyloP100		1.8
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: rs11713169; hg19: chr3-173384589;