chr3-174253013-G-T

Variant names:

• chr3-174253013-G-T
• rs9856717
• NM_001365925.2:c.707-22302G>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.707-22302G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,976 control chromosomes in the GnomAD database, including 4,099 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 0.22 (4099 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 2 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: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	NM_001365925.2	MANE Select	c.707-22302G>T		intron	N/A	NP_001352854.1	A0A8Q3SHM6
	NLGN1	NM_001365923.2		c.707-22302G>T		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-22302G>T		intron	N/A	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.707-22302G>T		intron	N/A	ENSP00000511841.1	A0A8Q3SHM6
	NLGN1	ENST00000415045.2	TSL:1	c.767-22302G>T		intron	N/A	ENSP00000410374.2	C9J4D3
	NLGN1	ENST00000361589.8	TSL:1	c.647-22302G>T		intron	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34101 AN: 151858 Hom.: 4104 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.224 AC: 34110 AN: 151976 Hom.: 4099 Cov.: 32 AF XY: 0.228 AC XY: 16903 AN XY: 74238

African (AFR) AF: 0.173 AC: 7178 AN: 41454

American (AMR) AF: 0.273 AC: 4165 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3470

East Asian (EAS) AF: 0.524 AC: 2705 AN: 5166

South Asian (SAS) AF: 0.165 AC: 794 AN: 4824

European-Finnish (FIN) AF: 0.256 AC: 2692 AN: 10496

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14917 AN: 67976

Other (OTH) AF: 0.232 AC: 491 AN: 2112

Alfa AF: 0.217 Hom.: 1871

Bravo AF: 0.227

Asia WGS AF: 0.319 AC: 1109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.31
PhyloP100		0.052
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: rs9856717; hg19: chr3-173970803;