3-174248948-C-T

Variant names:

• chr3-174248948-C-T
• rs13088246
• NM_001365925.2:c.707-26367C>T

Variant summary

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

The NM_001365925.2(NLGN1):​c.707-26367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,172 control chromosomes in the GnomAD database, including 3,498 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 0.21 (3498 hom., cov: 33)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.707-26367C>T		intron_variant	Intron 4 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-26367C>T		intron_variant	Intron 4 of 6		NM_001365925.2	ENSP00000511841.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31376 AN: 152052 Hom.: 3498 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.206 AC: 31380 AN: 152172 Hom.: 3498 Cov.: 33 AF XY: 0.207 AC XY: 15397 AN XY: 74384

African (AFR) AF: 0.153 AC: 6358 AN: 41528

American (AMR) AF: 0.254 AC: 3879 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3464

East Asian (EAS) AF: 0.497 AC: 2561 AN: 5158

South Asian (SAS) AF: 0.160 AC: 771 AN: 4816

European-Finnish (FIN) AF: 0.198 AC: 2094 AN: 10590

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14102 AN: 68004

Other (OTH) AF: 0.217 AC: 458 AN: 2114

Alfa AF: 0.208 Hom.: 5660

Bravo AF: 0.211

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.13
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: rs13088246; hg19: chr3-173966738;