dbSNP rs6786075: NLGN1:c.706+107249G>T (chr3-173915081-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Publications

2 publications found

Variant links:

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 links:

NLGN1-AS1 (HGNC:40676): (NLGN1 antisense RNA 1)

NLGN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365925.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLGN1	NM_001365925.2	MANE Select	c.706+107249G>T	intron	N/A	NP_001352854.1	A0A8Q3SHM6
NLGN1	NM_001365923.2		c.706+107249G>T	intron	N/A	NP_001352852.1
NLGN1	NM_001365924.2		c.706+107249G>T	intron	N/A	NP_001352853.1	A0A8Q3SHM6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLGN1	ENST00000695368.1	MANE Select	c.706+107249G>T	intron	N/A	ENSP00000511841.1	A0A8Q3SHM6
NLGN1	ENST00000415045.2	TSL:1	c.766+107249G>T	intron	N/A	ENSP00000410374.2	C9J4D3
NLGN1	ENST00000361589.8	TSL:1	c.646+107249G>T	intron	N/A	ENSP00000354541.4	Q8N2Q7-2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42757

AN:

151962

Hom.:

6787

Cov.:

show subpopulations

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:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.282

AC:

42812

AN:

152080

Hom.:

6813

Cov.:

AF XY:

0.281

AC XY:

20871

AN XY:

74340

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15240

AN:

67964

Other (OTH)

AF:

0.267

AC:

565

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1540

3079

4619

6158

7698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

1.6

(source)

DANN

Benign

0.34

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over