chr1-21616643-C-T

Position:

• chr1-21616643-C-T

Variant summary

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

The NM_002885.4(RAP1GAP):​c.291+663G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,106 control chromosomes in the GnomAD database, including 7,267 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 0.31 (7267 hom., cov: 33)
• Consequence: RAP1GAP NM_002885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

Genes affected

RAP1GAP (HGNC:9858): (RAP1 GTPase activating protein) This gene encodes a type of GTPase-activating-protein (GAP) that down-regulates the activity of the ras-related RAP1 protein. RAP1 acts as a molecular switch by cycling between an inactive GDP-bound form and an active GTP-bound form. The product of this gene, RAP1GAP, promotes the hydrolysis of bound GTP and hence returns RAP1 to the inactive state whereas other proteins, guanine nucleotide exchange factors (GEFs), act as RAP1 activators by facilitating the conversion of RAP1 from the GDP- to the GTP-bound form. In general, ras subfamily proteins, such as RAP1, play key roles in receptor-linked signaling pathways that control cell growth and differentiation. RAP1 plays a role in diverse processes such as cell proliferation, adhesion, differentiation, and embryogenesis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Aug 2011]

RAP1GAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GAP	NM_002885.4	c.291+663G>A		intron_variant		ENST00000374765.9	NP_002876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GAP	ENST00000374765.9	c.291+663G>A		intron_variant		1	NM_002885.4	ENSP00000363897.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46902 AN: 151988 Hom.: 7257 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.309 AC: 46931 AN: 152106 Hom.: 7267 Cov.: 33 AF XY: 0.308 AC XY: 22894 AN XY: 74374

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.284

Alfa AF: 0.317 Hom.: 10392

Bravo AF: 0.316

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.72

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: rs829417; hg19: chr1-21943136;