rs12337223

Variant names:

• chr9-123001958-G-A
• rs12337223
• NM_012197.4:c.1374+3192G>A

Variant summary

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

The NM_012197.4(RABGAP1):​c.1374+3192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,060 control chromosomes in the GnomAD database, including 2,914 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 0.11 (2914 hom., cov: 31)
• Consequence: RABGAP1 NM_012197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1	NM_012197.4	c.1374+3192G>A		intron_variant	Intron 10 of 25	ENST00000373647.9	NP_036329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1	ENST00000373647.9	c.1374+3192G>A		intron_variant	Intron 10 of 25	1	NM_012197.4	ENSP00000362751.4
RABGAP1	ENST00000456584.5	n.1170+3192G>A		intron_variant	Intron 11 of 27	2		ENSP00000414386.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16552 AN: 151942 Hom.: 2912 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.109 AC: 16574 AN: 152060 Hom.: 2914 Cov.: 31 AF XY: 0.105 AC XY: 7779 AN XY: 74344

African (AFR) AF: 0.373 AC: 15436 AN: 41414

American (AMR) AF: 0.0463 AC: 706 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 68016

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.0441 Hom.: 377

Bravo AF: 0.125

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.068
DANN	Benign	0.60
PhyloP100		-1.4
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: rs12337223; hg19: chr9-125764237;