rs10985840

Variant names:

• chr9-122954784-G-A
• rs10985840
• NM_012197.4:c.-49-2227G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_012197.4(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 NM_012197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
RABGAP1	NM_012197.4	c.-49-2227G>A		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.-49-2227G>A		intron_variant	Intron 1 of 25	1	NM_012197.4	ENSP00000362751.4

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

African (AFR) AF: 0.0821 AC: 3410 AN: 41516

American (AMR) AF: 0.0454 AC: 694 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4828

European-Finnish (FIN) AF: 0.0875 AC: 926 AN: 10578

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4488 AN: 68010

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0562 Hom.: 198

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
PhyloP100		-0.28
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: rs10985840; hg19: chr9-125717063;