rs10985840

Positions:

• chr9-122954784-G-A
• chr9-122954784-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373647.9(RABGAP1):​c.-49-2227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 152,200 control chromosomes in the GnomAD database, including 393 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 0.066 (393 hom., cov: 32)
• Consequence: RABGAP1 ENST00000373647.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1	NM_012197.4	c.-49-2227G>A		intron_variant		ENST00000373647.9	NP_036329.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1	ENST00000373647.9	c.-49-2227G>A		intron_variant		1	NM_012197.4	ENSP00000362751	P1

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10073 AN: 152082 Hom.: 392 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0663 AC: 10090 AN: 152200 Hom.: 393 Cov.: 32 AF XY: 0.0648 AC XY: 4824 AN XY: 74408

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0875

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0541 Hom.: 141

Bravo AF: 0.0642

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs10985840; hg19: chr9-125717063;