rs2290488

chrX-6227814-C-GchrX-6227814-C-T

Variant summary

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

The ENST00000275857.10(NLGN4X):c.-431G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 109,188 control chromosomes in the GnomAD database, including 3,992 homozygotes. There are 9,433 hemizygotes in GnomAD. 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 0.30 (3983 hom., 9424 hem., cov: 21)
  • Exomes 𝑓: 0.35 (9 hom. 9 hem.)
• Consequence: NLGN4X ENST00000275857.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

Genes affected

NLGN4X (HGNC:14287): (neuroligin 4 X-linked) This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to 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. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

LOC105373156 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLGN4X	NM_181332.3	c.-306+727G>C		intron_variant		ENST00000381095.8
LOC105373156	NR_136577.1	n.1457C>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLGN4X	ENST00000275857.10	c.-431G>C		5_prime_UTR_variant	1/6	1		P4
NLGN4X	ENST00000381095.8	c.-306+727G>C		intron_variant		1	NM_181332.3	P4
NLGN4X	ENST00000381092.1	c.-613+727G>C		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.301 AC: 32807 AN: 108983 Hom.: 3984 Cov.: 21 AF XY: 0.300 AC XY: 9404 AN XY: 31395

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.355 AC: 55 AN: 155 Hom.: 9 Cov.: 0 AF XY: 0.243 AC XY: 9 AN XY: 37

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.571

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.301 AC: 32825 AN: 109033 Hom.: 3983 Cov.: 21 AF XY: 0.300 AC XY: 9424 AN XY: 31455

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.318

Alfa AF: 0.315 Hom.: 2028

Bravo AF: 0.293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.25
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290488; hg19: chrX-6145855;