1-174221067-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001366446.1(RABGAP1L):c.234A>G(p.Gln78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,930 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: RABGAP1L NM_001366446.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.468

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-174221067-A-G is Benign according to our data. Variant chr1-174221067-A-G is described in ClinVar as [Benign]. Clinvar id is 2639569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.468 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABGAP1L	NM_001366446.1	c.234A>G	p.Gln78=	synonymous_variant	3/26	ENST00000681986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.234A>G	p.Gln78=	synonymous_variant	3/26		NM_001366446.1	P2

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00279

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00126 AC: 316 AN: 251240 Hom.: 1 AF XY: 0.00135 AC XY: 183 AN XY: 135774

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00215

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.00169 AC: 2474 AN: 1461658 Hom.: 4 Cov.: 30 AF XY: 0.00170 AC XY: 1238 AN XY: 727128

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00206

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00156 AC XY: 116 AN XY: 74452

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00279

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00129

EpiCase AF: 0.00180

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

RABGAP1L: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.22
Dann	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17854182; hg19: chr1-174190205;