rs11721044

Positions:

• chr3-173437333-T-C

Variant summary

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

The NM_001365925.2(NLGN1):​c.-321+39270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,130 control chromosomes in the GnomAD database, including 3,458 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 0.17 (3458 hom., cov: 32)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN1	NM_001365925.2	c.-321+39270T>C		intron_variant		ENST00000695368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN1	ENST00000695368.1	c.-321+39270T>C		intron_variant			NM_001365925.2	A1
NLGN1	ENST00000457714.5	c.-321+2255T>C		intron_variant		1		P2
NLGN1	ENST00000413821.1	c.-321+39270T>C		intron_variant		4
NLGN1	ENST00000423427.1	c.-321+40638T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26289 AN: 152010 Hom.: 3447 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.173 AC: 26322 AN: 152130 Hom.: 3458 Cov.: 32 AF XY: 0.168 AC XY: 12529 AN XY: 74384

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.187

Alfa AF: 0.121 Hom.: 810

Bravo AF: 0.186

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.72

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: rs11721044; hg19: chr3-173155123;