1-174583673-C-T

Position:

• chr1-174583673-C-T

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.1711-53702C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,100 control chromosomes in the GnomAD database, including 1,396 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 0.12 (1396 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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]

RABGAP1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.1711-53702C>T		intron_variant		ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.1711-53702C>T		intron_variant			NM_001366446.1	ENSP00000507884.1
RABGAP1L	ENST00000251507.8	c.1711-53702C>T		intron_variant		2		ENSP00000251507.4
RABGAP1L	ENST00000526253.1	n.326-53702C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17946 AN: 151982 Hom.: 1389 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.118 AC: 17960 AN: 152100 Hom.: 1396 Cov.: 32 AF XY: 0.121 AC XY: 8985 AN XY: 74318

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0246

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.124

Alfa AF: 0.144 Hom.: 1768

Bravo AF: 0.108

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.58

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: rs17301853; hg19: chr1-174552811; COSMIC: COSV52323586;