rs12078839

Variant names:

• chr1-174892350-C-G
• rs12078839
• NM_001366446.1:c.2341-65107C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000237249 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366446.1. 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
	RABGAP1L	NM_001366446.1	MANE Select	c.2341-65107C>G		intron	N/A	NP_001353375.1	A0A804HKD7
	RABGAP1L	NM_001366448.1		c.2341-65107C>G		intron	N/A	NP_001353377.1
	RABGAP1L	NM_014857.5		c.2341-65107C>G		intron	N/A	NP_055672.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	ENST00000681986.1	MANE Select	c.2341-65107C>G		intron	N/A	ENSP00000507884.1	A0A804HKD7
	RABGAP1L	ENST00000347255.6	TSL:1	c.322-65107C>G		intron	N/A	ENSP00000281844.5	Q5R372-5
	RABGAP1L	ENST00000489615.5	TSL:1	c.298-65107C>G		intron	N/A	ENSP00000420660.1	Q5R372-8

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

African (AFR) AF: 0.563 AC: 2226 AN: 3956

American (AMR) AF: 0.262 AC: 2364 AN: 9014

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1275 AN: 4326

East Asian (EAS) AF: 0.0575 AC: 407 AN: 7082

South Asian (SAS) AF: 0.212 AC: 8250 AN: 38902

European-Finnish (FIN) AF: 0.284 AC: 2621 AN: 9222

Middle Eastern (MID) AF: 0.232 AC: 151 AN: 650

European-Non Finnish (NFE) AF: 0.232 AC: 27021 AN: 116534

Other (OTH) AF: 0.249 AC: 2431 AN: 9772

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

African (AFR) AF: 0.586 AC: 24320 AN: 41512

American (AMR) AF: 0.295 AC: 4506 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.0693 AC: 360 AN: 5192

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4830

European-Finnish (FIN) AF: 0.279 AC: 2950 AN: 10570

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15939 AN: 68014

Other (OTH) AF: 0.305 AC: 645 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.33
PhyloP100		-1.9
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: rs12078839; hg19: chr1-174861487;