rs17710

Positions:

• chr17-7240675-A-T

Variant summary

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

The NM_007278.2(GABARAP):​c.*179T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 579,132 control chromosomes in the GnomAD database, including 5,701 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 0.11 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4600 hom.)
• Consequence: GABARAP NM_007278.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

Genes affected

GABARAP (HGNC:4067): (GABA type A receptor-associated protein) Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton. [provided by RefSeq, Jul 2008]

PHF23 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABARAP	NM_007278.2	c.*179T>A		3_prime_UTR_variant	4/4	ENST00000302386.10
PHF23	XM_024450938.2	c.-1044T>A		5_prime_UTR_variant	1/5
PHF23	XM_047436728.1	c.-1044T>A		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABARAP	ENST00000302386.10	c.*179T>A		3_prime_UTR_variant	4/4	1	NM_007278.2	P1
GABARAP	ENST00000571129.5	c.*179T>A		3_prime_UTR_variant	4/4	2
GABARAP	ENST00000577035.5	c.*179T>A		3_prime_UTR_variant	4/4	2
GABARAP	ENST00000570856.1	c.*343T>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15990 AN: 152076 Hom.: 1098 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0429

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.136 AC: 58147 AN: 426938 Hom.: 4600 Cov.: 3 AF XY: 0.141 AC XY: 31815 AN XY: 226296

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.0578

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.105 AC: 15989 AN: 152194 Hom.: 1101 Cov.: 32 AF XY: 0.109 AC XY: 8093 AN XY: 74408

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0704

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.107

Alfa AF: 0.132 Hom.: 186

Bravo AF: 0.0877

Asia WGS AF: 0.108 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs17710; hg19: chr17-7143994;