1-170532026-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_125958.1(GORAB-AS1):n.162+422A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,277,734 control chromosomes in the GnomAD database, including 33,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3862 hom., cov: 32)
  • Exomes 𝑓: 0.21 (29647 hom.)
• Consequence: GORAB-AS1 NR_125958.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.56

Genes affected

GORAB-AS1 (HGNC:54051): (GORAB antisense RNA 1)

GORAB (HGNC:25676): (golgin, RAB6 interacting) This gene encodes a member of the golgin family, a group of coiled-coil proteins localized to the Golgi. The encoded protein may function in the secretory pathway. The encoded protein, which also localizes to the cytoplasm, was identified by interactions with the N-terminal kinase-like protein, and thus it may function in mitosis. Mutations in this gene have been associated with geroderma osteodysplastica. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-170532026-T-C is Benign according to our data. Variant chr1-170532026-T-C is described in ClinVar as [Benign]. Clinvar id is 1241712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GORAB-AS1	NR_125958.1	n.162+422A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GORAB-AS1	ENST00000456083.5	n.200+422A>G		intron_variant, non_coding_transcript_variant		3
GORAB	ENST00000685976.1	n.166+42T>C		intron_variant, non_coding_transcript_variant
GORAB-AS1	ENST00000421020.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30760 AN: 151954 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.211 AC: 237713 AN: 1125662 Hom.: 29647 Cov.: 15 AF XY: 0.208 AC XY: 119305 AN XY: 572788

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.203 AC: 30801 AN: 152072 Hom.: 3862 Cov.: 32 AF XY: 0.211 AC XY: 15704 AN XY: 74326

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.183

Alfa AF: 0.194 Hom.: 6174

Bravo AF: 0.206

Asia WGS AF: 0.380 AC: 1321 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.010
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16863397; hg19: chr1-170501167;