rs6445137

Variant names:

• chr3-174057494-C-T
• rs6445137
• NM_001365925.2:c.707-217821C>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.707-217821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,018 control chromosomes in the GnomAD database, including 1,827 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 0.15 (1827 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: NLGN1 NM_001365925.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 3 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]

RN7SKP234 (HGNC:45958): (RN7SK pseudogene 234)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	NM_001365925.2	MANE Select	c.707-217821C>T		intron	N/A	NP_001352854.1
	NLGN1	NM_001365923.2		c.707-217821C>T		intron	N/A	NP_001352852.1
	NLGN1	NM_001365924.2		c.707-217821C>T		intron	N/A	NP_001352853.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLGN1	ENST00000695368.1	MANE Select	c.707-217821C>T		intron	N/A	ENSP00000511841.1
	NLGN1	ENST00000415045.2	TSL:1	c.767-217821C>T		intron	N/A	ENSP00000410374.2
	NLGN1	ENST00000361589.8	TSL:1	c.647-217821C>T		intron	N/A	ENSP00000354541.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23114 AN: 151886 Hom.: 1827 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0945

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.152 AC: 23121 AN: 152004 Hom.: 1827 Cov.: 32 AF XY: 0.150 AC XY: 11135 AN XY: 74320

African (AFR) AF: 0.155 AC: 6450 AN: 41480

American (AMR) AF: 0.102 AC: 1551 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3466

East Asian (EAS) AF: 0.182 AC: 938 AN: 5154

South Asian (SAS) AF: 0.0950 AC: 458 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10592

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11046 AN: 67926

Other (OTH) AF: 0.147 AC: 310 AN: 2108

Alfa AF: 0.155 Hom.: 1032

Bravo AF: 0.148

Asia WGS AF: 0.116 AC: 404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-0.38
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: rs6445137; hg19: chr3-173775284;