X-154408969-C-T

Variant names:

• chrX-154408969-C-T
• rs2070807
• ENST00000369808.7:c.-499G>A

Variant summary

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

The NM_006730.4(DNASE1L1):​c.-499G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 248,205 control chromosomes in the GnomAD database, including 7,448 homozygotes. There are 15,078 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 0.28 (5886 hom., 8780 hem., cov: 23)
  • Exomes 𝑓: 0.15 (1562 hom. 6298 hem.)
• Consequence: DNASE1L1 NM_006730.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

Genes affected

DNASE1L1 (HGNC:2957): (deoxyribonuclease 1 like 1) This gene encodes a deoxyribonuclease protein that shows high sequence similarity to DNase I. The encoded protein is localized to the endoplasmic reticulum and modified by N-linked glycosylation. Alternate transcriptional splice variants encoding the same protein have been observed. [provided by RefSeq, Jan 2015]

RPL10 (HGNC:10298): (ribosomal protein L10) This gene encodes a ribosomal protein that is a component of the 60S ribosome subunit. The related protein in chicken can bind to c-Jun and can repress c-Jun-mediated transcriptional activation. Some studies have detected an association between variation in this gene and autism spectrum disorders, though others do not detect this relationship. There are multiple pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNASE1L1	NM_001303620.2	c.-88+143G>A		intron_variant	Intron 1 of 7	ENST00000369807.6	NP_001290549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNASE1L1	ENST00000369807.6	c.-88+143G>A		intron_variant	Intron 1 of 7	1	NM_001303620.2	ENSP00000358822.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 31056 AN: 111115 Hom.: 5872 Cov.: 23 AF XY: 0.262 AC XY: 8738 AN XY: 33349

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.00880

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0763

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.146 AC: 20064 AN: 137038 Hom.: 1562 Cov.: 0 AF XY: 0.148 AC XY: 6298 AN XY: 42660

Gnomad4 AFR exome AF: 0.686

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.0674

Gnomad4 EAS exome AF: 0.0670

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.280 AC: 31122 AN: 111167 Hom.: 5886 Cov.: 23 AF XY: 0.263 AC XY: 8780 AN XY: 33411

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0897

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.250

Alfa AF: 0.147 Hom.: 4079

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2070807; hg19: chrX-153637305;