rs17331728

Variant names:

• chrX-102699540-G-C
• rs17331728
• NM_001199818.1:c.-479-14242G>C

Variant summary

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

The NM_001199818.1(ARMCX5-GPRASP2):​c.-479-14242G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 111,391 control chromosomes in the GnomAD database, including 583 homozygotes. There are 3,240 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 0.10 (583 hom., 3240 hem., cov: 23)
• Consequence: ARMCX5-GPRASP2 NM_001199818.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 0 publications found

Genes affected

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ENSG00000271147 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX5-GPRASP2	NM_001199818.1	c.-479-14242G>C		intron_variant	Intron 4 of 6		NP_001186747.1
ARMCX5-GPRASP2	NM_001350268.2	c.-965-14242G>C		intron_variant	Intron 2 of 7		NP_001337197.1
ARMCX5-GPRASP2	NR_146584.3	n.650-14242G>C		intron_variant	Intron 4 of 18
ARMCX5-GPRASP2	NR_146585.2	n.151-14242G>C		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000271147	ENST00000486740.6	n.409-14242G>C		intron_variant	Intron 4 of 6	3
ENSG00000271147	ENST00000602366.5	n.495-14242G>C		intron_variant	Intron 2 of 3	4
ENSG00000271147	ENST00000602463.5	n.370-14242G>C		intron_variant	Intron 3 of 5	4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 11304 AN: 111349 Hom.: 583 Cov.: 23

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0952

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.000553

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 11300 AN: 111391 Hom.: 583 Cov.: 23 AF XY: 0.0963 AC XY: 3240 AN XY: 33637

African (AFR) AF: 0.0221 AC: 682 AN: 30794

American (AMR) AF: 0.0893 AC: 941 AN: 10535

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 343 AN: 2645

East Asian (EAS) AF: 0.000554 AC: 2 AN: 3607

South Asian (SAS) AF: 0.0317 AC: 85 AN: 2679

European-Finnish (FIN) AF: 0.159 AC: 913 AN: 5732

Middle Eastern (MID) AF: 0.130 AC: 28 AN: 216

European-Non Finnish (NFE) AF: 0.152 AC: 8066 AN: 52985

Other (OTH) AF: 0.116 AC: 175 AN: 1515

Alfa AF: 0.124 Hom.: 817

Bravo AF: 0.0946

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		0.060

Splicing

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

Other links and lift over

dbSNP: rs17331728; hg19: chrX-101954468;