1-170533376-A-G

Variant names:

• chr1-170533376-A-G
• rs1412892
• NM_152281.3:c.61+1092A>G

Variant summary

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

The NM_152281.3(GORAB):​c.61+1092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 292,008 control chromosomes in the GnomAD database, including 135,640 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 0.94 (67273 hom., cov: 31)
  • Exomes 𝑓: 0.99 (68367 hom.)
• Consequence: GORAB NM_152281.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 3 publications found

Genes affected

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GORAB	NM_152281.3	MANE Select	c.61+1092A>G		intron	N/A	NP_689494.3
	GORAB	NM_001410894.1		c.10+1143A>G		intron	N/A	NP_001397823.1
	GORAB	NM_001146039.2		c.61+1092A>G		intron	N/A	NP_001139511.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GORAB	ENST00000367763.8	TSL:2 MANE Select	c.61+1092A>G		intron	N/A	ENSP00000356737.4
	GORAB	ENST00000367762.2	TSL:1	c.61+1092A>G		intron	N/A	ENSP00000356736.2
	GORAB	ENST00000498166.6	TSL:1	n.62-88A>G		intron	N/A	ENSP00000473336.2

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142282 AN: 152134 Hom.: 67237 Cov.: 31

Gnomad AFR AF: 0.779

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.951

GnomAD4 exome AF: 0.988 AC: 138115 AN: 139756 Hom.: 68367 AF XY: 0.990 AC XY: 76182 AN XY: 76914

African (AFR) AF: 0.781 AC: 4058 AN: 5196

American (AMR) AF: 0.986 AC: 14153 AN: 14354

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3263 AN: 3376

East Asian (EAS) AF: 1.00 AC: 8021 AN: 8022

South Asian (SAS) AF: 1.00 AC: 28773 AN: 28784

European-Finnish (FIN) AF: 1.00 AC: 5552 AN: 5552

Middle Eastern (MID) AF: 0.995 AC: 627 AN: 630

European-Non Finnish (NFE) AF: 0.999 AC: 67331 AN: 67404

Other (OTH) AF: 0.984 AC: 6337 AN: 6438

GnomAD4 genome AF: 0.935 AC: 142371 AN: 152252 Hom.: 67273 Cov.: 31 AF XY: 0.937 AC XY: 69749 AN XY: 74438

African (AFR) AF: 0.779 AC: 32325 AN: 41496

American (AMR) AF: 0.975 AC: 14930 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3347 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 0.999 AC: 4825 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67940 AN: 68042

Other (OTH) AF: 0.952 AC: 2012 AN: 2114

Alfa AF: 0.959 Hom.: 8587

Bravo AF: 0.927

Asia WGS AF: 0.985 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.31
PhyloP100		-0.67
Mutation Taster		=100/0	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: rs1412892; hg19: chr1-170502517;