1-174835984-T-G

Variant names:

• chr1-174835984-T-G
• rs1754352
• NM_001366446.1:c.2340+24024T>G

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.2340+24024T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,080 control chromosomes in the GnomAD database, including 34,245 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 0.65 (34245 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.2340+24024T>G		intron_variant	Intron 19 of 25	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.2340+24024T>G		intron_variant	Intron 19 of 25		NM_001366446.1	ENSP00000507884.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98215 AN: 151962 Hom.: 34249 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.646 AC: 98244 AN: 152080 Hom.: 34245 Cov.: 32 AF XY: 0.648 AC XY: 48152 AN XY: 74330

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.684

Alfa AF: 0.639 Hom.: 4437

Bravo AF: 0.631

Asia WGS AF: 0.783 AC: 2724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.4
DANN	Benign	0.88

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: rs1754352; hg19: chr1-174805122;