1-174982141-C-T

Variant names:

• chr1-174982141-C-T
• rs2285210
• NM_001366446.1:c.2734-693C>T

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.2734-693C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,108 control chromosomes in the GnomAD database, including 44,681 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 0.76 (44681 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.2734-693C>T		intron_variant	Intron 23 of 25	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.2734-693C>T		intron_variant	Intron 23 of 25		NM_001366446.1	ENSP00000507884.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115044 AN: 151988 Hom.: 44620 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.757 AC: 115164 AN: 152108 Hom.: 44681 Cov.: 32 AF XY: 0.754 AC XY: 56032 AN XY: 74350

African (AFR) AF: 0.937 AC: 38927 AN: 41538

American (AMR) AF: 0.627 AC: 9579 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2602 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3260 AN: 5164

South Asian (SAS) AF: 0.676 AC: 3260 AN: 4826

European-Finnish (FIN) AF: 0.731 AC: 7728 AN: 10568

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47406 AN: 67952

Other (OTH) AF: 0.749 AC: 1578 AN: 2106

Alfa AF: 0.713 Hom.: 19686

Bravo AF: 0.757

Asia WGS AF: 0.682 AC: 2377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.57
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2285210; hg19: chr1-174951278;