chr1-174228663-C-T

Variant names:

• chr1-174228663-C-T
• rs10489254
• NM_001366446.1:c.332-2482C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	NM_001366446.1	MANE Select	c.332-2482C>T		intron	N/A	NP_001353375.1
	RABGAP1L	NM_001366448.1		c.332-2482C>T		intron	N/A	NP_001353377.1
	RABGAP1L	NM_014857.5		c.332-2482C>T		intron	N/A	NP_055672.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	ENST00000681986.1	MANE Select	c.332-2482C>T		intron	N/A	ENSP00000507884.1
	RABGAP1L	ENST00000357444.10	TSL:1	c.221-2482C>T		intron	N/A	ENSP00000350027.6
	RABGAP1L	ENST00000457696.1	TSL:1	c.332-2482C>T		intron	N/A	ENSP00000403136.1

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

African (AFR) AF: 0.0530 AC: 2198 AN: 41500

American (AMR) AF: 0.0632 AC: 965 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 255 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1642 AN: 5170

South Asian (SAS) AF: 0.107 AC: 517 AN: 4822

European-Finnish (FIN) AF: 0.0821 AC: 864 AN: 10528

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4331 AN: 67990

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0689 Hom.: 1081

Bravo AF: 0.0723

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.49
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: rs10489254; hg19: chr1-174197801;