rs10489254

chr1-174228663-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001366446.1(RABGAP1L):c.332-2482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,062 control chromosomes in the GnomAD database, including 598 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 0.073 (598 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABGAP1L	NM_001366446.1	c.332-2482C>T		intron_variant		ENST00000681986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.332-2482C>T		intron_variant			NM_001366446.1	P2

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11030 AN: 151944 Hom.: 599 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0725 AC: 11031 AN: 152062 Hom.: 598 Cov.: 32 AF XY: 0.0749 AC XY: 5568 AN XY: 74300

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0702 Hom.: 759

Bravo AF: 0.0723

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	14
Dann	Benign	0.79

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: rs10489254; hg19: chr1-174197801;