chr3-174135994-G-A

Position:

• chr3-174135994-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.707-139321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,856 control chromosomes in the GnomAD database, including 3,306 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 0.20 (3306 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.707-139321G>A		intron_variant		ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.707-139321G>A		intron_variant			NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000415045.2	c.767-139321G>A		intron_variant		1		ENSP00000410374.2
NLGN1	ENST00000361589.8	c.647-139321G>A		intron_variant		1		ENSP00000354541.4
NLGN1	ENST00000457714.5	c.647-139321G>A		intron_variant		1		ENSP00000392500.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29985 AN: 151738 Hom.: 3308 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.198 AC: 30014 AN: 151856 Hom.: 3306 Cov.: 32 AF XY: 0.199 AC XY: 14761 AN XY: 74230

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.182

Alfa AF: 0.157 Hom.: 2683

Bravo AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6445141; hg19: chr3-173853784;