chr9-122947044-A-G

Variant names:

• chr9-122947044-A-G
• rs10818768
• NM_012197.4:c.-50+5951A>G

Variant summary

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

The NM_012197.4(RABGAP1):​c.-50+5951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,946 control chromosomes in the GnomAD database, including 13,436 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 0.38 (13436 hom., cov: 31)
• Consequence: RABGAP1 NM_012197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1	NM_012197.4	c.-50+5951A>G		intron_variant	Intron 1 of 25	ENST00000373647.9	NP_036329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1	ENST00000373647.9	c.-50+5951A>G		intron_variant	Intron 1 of 25	1	NM_012197.4	ENSP00000362751.4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57622 AN: 151828 Hom.: 13441 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.379 AC: 57611 AN: 151946 Hom.: 13436 Cov.: 31 AF XY: 0.382 AC XY: 28375 AN XY: 74260

African (AFR) AF: 0.101 AC: 4182 AN: 41508

American (AMR) AF: 0.413 AC: 6314 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1771 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1437 AN: 5174

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5692 AN: 10504

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33945 AN: 67886

Other (OTH) AF: 0.390 AC: 821 AN: 2106

Alfa AF: 0.460 Hom.: 33010

Bravo AF: 0.352

Asia WGS AF: 0.401 AC: 1396 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.55
PhyloP100		-0.47
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: rs10818768; hg19: chr9-125709323;