NM_001366446.1:c.1711-53702C>T

Variant names:

• chr1-174583673-C-T
• rs17301853
• NM_001366446.1:c.1711-53702C>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.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
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	NM_001366446.1	MANE Select	c.1711-53702C>T		intron	N/A	NP_001353375.1	A0A804HKD7
	RABGAP1L	NM_001366448.1		c.1711-53702C>T		intron	N/A	NP_001353377.1
	RABGAP1L	NM_014857.5		c.1711-53702C>T		intron	N/A	NP_055672.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	ENST00000681986.1	MANE Select	c.1711-53702C>T		intron	N/A	ENSP00000507884.1	A0A804HKD7
	RABGAP1L	ENST00000251507.8	TSL:2	c.1711-53702C>T		intron	N/A	ENSP00000251507.4	Q5R372-1
	RABGAP1L	ENST00000526253.1	TSL:5	n.326-53702C>T		intron	N/A

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

African (AFR) AF: 0.0326 AC: 1353 AN: 41520

American (AMR) AF: 0.135 AC: 2065 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3470

East Asian (EAS) AF: 0.0246 AC: 127 AN: 5172

South Asian (SAS) AF: 0.170 AC: 817 AN: 4804

European-Finnish (FIN) AF: 0.185 AC: 1952 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10539 AN: 67992

Other (OTH) AF: 0.124 AC: 262 AN: 2114

Alfa AF: 0.139 Hom.: 2419

Bravo AF: 0.108

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-0.37
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: rs17301853; hg19: chr1-174552811; COSMIC: COSV52323586;