rs11721044

Variant names:

• chr3-173437333-T-C
• rs11721044
• NM_001365925.2:c.-321+39270T>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.-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
• 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=-0.91).
• 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 rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.-321+39270T>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.-321+39270T>C		intron_variant	Intron 1 of 6		NM_001365925.2	ENSP00000511841.1
NLGN1	ENST00000457714.5	c.-321+2255T>C		intron_variant	Intron 2 of 6	1		ENSP00000392500.1
NLGN1	ENST00000423427.1	c.-321+40638T>C		intron_variant	Intron 1 of 1	4		ENSP00000407255.1
NLGN1	ENST00000413821.1	c.-321+39270T>C		intron_variant	Intron 1 of 1	4		ENSP00000401843.1

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

African (AFR) AF: 0.373 AC: 15468 AN: 41430

American (AMR) AF: 0.110 AC: 1683 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3468

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5184

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4826

European-Finnish (FIN) AF: 0.0609 AC: 646 AN: 10608

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7099 AN: 68000

Other (OTH) AF: 0.187 AC: 396 AN: 2116

Alfa AF: 0.121 Hom.: 876

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
PhyloP100		-0.91
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: rs11721044; hg19: chr3-173155123;