rs12078839

Positions:

• chr1-174892350-C-G

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.2341-65107C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 351,648 control chromosomes in the GnomAD database, including 16,648 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 0.34 (10600 hom., cov: 33)
  • Exomes 𝑓: 0.23 (6048 hom.)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

RABGAP1L (HGNC:24663): (RAB GTPase activating protein 1 like) Enables GTPase activator activity and small GTPase binding activity. Acts upstream of or within regulation of protein localization. Located in Golgi apparatus; early endosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RABGAP1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.2341-65107C>G		intron_variant		ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.2341-65107C>G		intron_variant			NM_001366446.1	ENSP00000507884.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51214 AN: 152072 Hom.: 10571 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0688

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.234 AC: 46746 AN: 199458 Hom.: 6048 AF XY: 0.228 AC XY: 25854 AN XY: 113388

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.0575

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.337 AC: 51302 AN: 152190 Hom.: 10600 Cov.: 33 AF XY: 0.337 AC XY: 25070 AN XY: 74402

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.0693

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.305

Alfa AF: 0.294 Hom.: 1008

Bravo AF: 0.348

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.33

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: rs12078839; hg19: chr1-174861487;