rs7638716

Variant names:

• chr3-173695729-A-G
• rs7638716
• NM_001365925.2:c.553+90136A>G

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+90136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 152,248 control chromosomes in the GnomAD database, including 825 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 0.087 (825 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.553+90136A>G		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+90136A>G		intron_variant	Intron 3 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000415045.2	c.553+90136A>G		intron_variant	Intron 3 of 7	1		ENSP00000410374.2
NLGN1	ENST00000361589.8	c.493+90638A>G		intron_variant	Intron 2 of 5	1		ENSP00000354541.4
NLGN1	ENST00000457714.5	c.493+90638A>G		intron_variant	Intron 3 of 6	1		ENSP00000392500.1

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13151 AN: 152130 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0827

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

GnomAD4 genome AF: 0.0867 AC: 13194 AN: 152248 Hom.: 825 Cov.: 32 AF XY: 0.0867 AC XY: 6457 AN XY: 74434

African (AFR) AF: 0.166 AC: 6878 AN: 41520

American (AMR) AF: 0.126 AC: 1927 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.0556 AC: 288 AN: 5182

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4828

European-Finnish (FIN) AF: 0.0370 AC: 392 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0436 AC: 2969 AN: 68030

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0614 Hom.: 376

Bravo AF: 0.0990

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.016
DANN	Benign	0.33
PhyloP100		-2.1
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: rs7638716; hg19: chr3-173413519;