rs6786075

Variant names:

• chr3-173915081-G-T
• rs6786075
• NM_001365925.2:c.706+107249G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365925.2(NLGN1):​c.706+107249G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,084 control chromosomes in the GnomAD database, including 6,813 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 0.28 (6813 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• 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-AS1 (HGNC:40676): (NLGN1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLGN1	NM_001365925.2	c.706+107249G>T		intron_variant	Intron 4 of 6	ENST00000695368.1	NP_001352854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLGN1	ENST00000695368.1	c.706+107249G>T		intron_variant	Intron 4 of 6		NM_001365925.2	ENSP00000511841.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42757 AN: 151962 Hom.: 6787 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.282 AC: 42812 AN: 152080 Hom.: 6813 Cov.: 33 AF XY: 0.281 AC XY: 20871 AN XY: 74340

African (AFR) AF: 0.426 AC: 17689 AN: 41482

American (AMR) AF: 0.176 AC: 2692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5166

South Asian (SAS) AF: 0.189 AC: 911 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2887 AN: 10574

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15240 AN: 67964

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.237 Hom.: 2434

Bravo AF: 0.280

Asia WGS AF: 0.254 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.34
PhyloP100		0.11
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: rs6786075; hg19: chr3-173632871;