3-174098520-T-C

Variant names:

• chr3-174098520-T-C
• rs7623402
• NM_001365925.2:c.707-176795T>C

Variant summary

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

The ENST00000695368.1(NLGN1):​c.707-176795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,030 control chromosomes in the GnomAD database, including 7,583 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 0.28 (7583 hom., cov: 32)
• Consequence: NLGN1 ENST00000695368.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000695368.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	NM_001365925.2	MANE Select	c.707-176795T>C		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.707-176795T>C		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-176795T>C		intron	N/A	NP_001352853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.707-176795T>C		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.767-176795T>C		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.647-176795T>C		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42051 AN: 151910 Hom.: 7559 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.277 AC: 42129 AN: 152030 Hom.: 7583 Cov.: 32 AF XY: 0.275 AC XY: 20452 AN XY: 74316

African (AFR) AF: 0.519 AC: 21507 AN: 41434

American (AMR) AF: 0.166 AC: 2540 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1141 AN: 5178

South Asian (SAS) AF: 0.186 AC: 898 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2394 AN: 10580

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.179 AC: 12181 AN: 67966

Other (OTH) AF: 0.245 AC: 518 AN: 2110

Alfa AF: 0.261 Hom.: 1542

Bravo AF: 0.284

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		-0.63
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: rs7623402; hg19: chr3-173816310;