NM_001004051.4:c.-366A>G

Variant names:

• chrX-102714234-A-G
• rs2073118
• NM_001004051.4:c.-366A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004051.4(GPRASP2):​c.-366A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 111,396 control chromosomes in the GnomAD database, including 658 homozygotes. There are 3,612 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (657 hom., 3607 hem., cov: 23)
  • Exomes 𝑓: 0.055 (1 hom. 5 hem.)
• Consequence: GPRASP2 NM_001004051.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490
• Publications: 1 publications found

Genes affected

GPRASP2 (HGNC:25169): (G protein-coupled receptor associated sorting protein 2) The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-102714234-A-G is Benign according to our data. Variant chrX-102714234-A-G is described in ClinVar as Benign. ClinVar VariationId is 1226940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP2	NM_001004051.4	MANE Select	c.-366A>G		5_prime_UTR	Exon 4 of 5	NP_001004051.1	Q96D09
	GPRASP2	NM_001184874.3		c.-494A>G		5_prime_UTR	Exon 4 of 5	NP_001171803.1	Q96D09
	GPRASP2	NM_001184875.3		c.-494A>G		5_prime_UTR	Exon 3 of 4	NP_001171804.1	Q96D09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRASP2	ENST00000483720.7	TSL:2 MANE Select	c.-366A>G		5_prime_UTR	Exon 4 of 5	ENSP00000507692.1	Q96D09
	GPRASP2	ENST00000332262.10	TSL:1	c.-366A>G		5_prime_UTR	Exon 3 of 4	ENSP00000339057.3	Q96D09
	ARMCX5-GPRASP2	ENST00000652409.1		c.-788A>G		5_prime_UTR	Exon 4 of 8	ENSP00000498643.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 12672 AN: 111032 Hom.: 655 Cov.: 23

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0802

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0548 AC: 17 AN: 310 Hom.: 1 Cov.: 0 AF XY: 0.0595 AC XY: 5 AN XY: 84

African (AFR) AF: 0.00 AC: 0 AN: 1

American (AMR) AF: 0.00 AC: 0 AN: 13

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 5

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1

European-Non Finnish (NFE) AF: 0.0542 AC: 15 AN: 277

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.114 AC: 12680 AN: 111086 Hom.: 657 Cov.: 23 AF XY: 0.108 AC XY: 3607 AN XY: 33350

African (AFR) AF: 0.175 AC: 5334 AN: 30501

American (AMR) AF: 0.0592 AC: 625 AN: 10551

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 187 AN: 2637

East Asian (EAS) AF: 0.213 AC: 741 AN: 3483

South Asian (SAS) AF: 0.138 AC: 359 AN: 2601

European-Finnish (FIN) AF: 0.133 AC: 791 AN: 5937

Middle Eastern (MID) AF: 0.0741 AC: 16 AN: 216

European-Non Finnish (NFE) AF: 0.0841 AC: 4453 AN: 52976

Other (OTH) AF: 0.110 AC: 165 AN: 1502

Alfa AF: 0.107 Hom.: 585

Bravo AF: 0.112

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.72
PhyloP100		-0.049
Mutation Taster		=300/0	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: rs2073118; hg19: chrX-101969162;