chr3-173600062-T-C

Variant names:

• chr3-173600062-T-C
• rs16828127
• NM_001365925.2:c.-320-4217T>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.-320-4217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 152,076 control chromosomes in the GnomAD database, including 786 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 0.094 (786 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-320-4217T>C		intron_variant	Intron 1 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.-320-4217T>C		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14312 AN: 151956 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0941 AC: 14314 AN: 152076 Hom.: 786 Cov.: 32 AF XY: 0.0997 AC XY: 7412 AN XY: 74350

African (AFR) AF: 0.0622 AC: 2583 AN: 41522

American (AMR) AF: 0.109 AC: 1659 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.165 AC: 849 AN: 5154

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4808

European-Finnish (FIN) AF: 0.122 AC: 1289 AN: 10600

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0912 AC: 6202 AN: 67968

Other (OTH) AF: 0.101 AC: 214 AN: 2110

Alfa AF: 0.0950 Hom.: 2148

Bravo AF: 0.0903

Asia WGS AF: 0.171 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.85
PhyloP100		0.22
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: rs16828127; hg19: chr3-173317852;