chr9-122975244-T-C

Variant names:

• chr9-122975244-T-C
• rs618746
• NM_012197.4:c.151-9241T>C

Variant summary

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

The NM_012197.4(RABGAP1):​c.151-9241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,154 control chromosomes in the GnomAD database, including 36,833 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 0.62 (36833 hom., cov: 31)
• Consequence: RABGAP1 NM_012197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 3 publications found

Genes affected

RABGAP1 (HGNC:17155): (RAB GTPase activating protein 1) Enables GTPase activator activity and small GTPase binding activity. Involved in regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RABGAP1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012197.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1	NM_012197.4	MANE Select	c.151-9241T>C		intron	N/A	NP_036329.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1	ENST00000373647.9	TSL:1 MANE Select	c.151-9241T>C		intron	N/A	ENSP00000362751.4
	RABGAP1	ENST00000402311.5	TSL:4	c.151-9241T>C		intron	N/A	ENSP00000384119.1
	RABGAP1	ENST00000317419.7	TSL:3	n.274-9241T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95116 AN: 152036 Hom.: 36850 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.625 AC: 95087 AN: 152154 Hom.: 36833 Cov.: 31 AF XY: 0.623 AC XY: 46339 AN XY: 74380

African (AFR) AF: 0.173 AC: 7181 AN: 41486

American (AMR) AF: 0.628 AC: 9602 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2951 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1546 AN: 5172

South Asian (SAS) AF: 0.808 AC: 3897 AN: 4824

European-Finnish (FIN) AF: 0.818 AC: 8661 AN: 10582

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58800 AN: 68020

Other (OTH) AF: 0.659 AC: 1392 AN: 2112

Alfa AF: 0.807 Hom.: 36548

Bravo AF: 0.584

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.70
PhyloP100		-0.18
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: rs618746; hg19: chr9-125737523;