9-123070600-T-C

Position:

• chr9-123070600-T-C

Variant summary

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

The NM_012197.4(RABGAP1):​c.1983+176T>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 152,138 control chromosomes in the GnomAD database, including 36,824 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 (36824 hom., cov: 32)
• Consequence: RABGAP1 NM_012197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABGAP1	NM_012197.4	c.1983+176T>C		intron_variant		ENST00000373647.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABGAP1	ENST00000373647.9	c.1983+176T>C		intron_variant		1	NM_012197.4	P1
RABGAP1	ENST00000456584.5	c.*119+176T>C		intron_variant, NMD_transcript_variant		2
RABGAP1	ENST00000475607.1	n.405+176T>C		intron_variant, non_coding_transcript_variant		4
RABGAP1	ENST00000493854.5	n.423+176T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95042 AN: 152020 Hom.: 36839 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.865

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: 95017 AN: 152138 Hom.: 36824 Cov.: 32 AF XY: 0.623 AC XY: 46331 AN XY: 74402

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.659

Alfa AF: 0.697 Hom.: 5741

Bravo AF: 0.583

Asia WGS AF: 0.512 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.39

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: rs803733; hg19: chr9-125832879;