rs7976407

Positions:

• chr12-113130992-A-G

Variant summary

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

The NM_001301202.2(RASAL1):​c.66-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,440,484 control chromosomes in the GnomAD database, including 10,189 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.14 (1668 hom., cov: 31)
  • Exomes 𝑓: 0.10 (8521 hom.)
• Consequence: RASAL1 NM_001301202.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

Genes affected

RASAL1 (HGNC:9873): (RAS protein activator like 1) The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. These proteins stimulate the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. This particular family member contains domains which are characteristic of the GAP1 subfamily of RasGAP proteins but, in contrast to the other GAP1 family members, this protein is strongly and selectively expressed in endocrine tissues. Alternatively spliced transcript variants that encode different isoforms have been described [provided by RefSeq, Jul 2010]

RASAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASAL1	NM_001301202.2	c.66-51T>C		intron_variant		ENST00000548055.2	NP_001288131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASAL1	ENST00000548055.2	c.66-51T>C		intron_variant		1	NM_001301202.2	ENSP00000448510.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20498 AN: 151884 Hom.: 1651 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.123 AC: 28813 AN: 234592 Hom.: 2152 AF XY: 0.124 AC XY: 15641 AN XY: 126422

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.0959

Gnomad NFE exome AF: 0.0840

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.104 AC: 134572 AN: 1288482 Hom.: 8521 Cov.: 18 AF XY: 0.107 AC XY: 69389 AN XY: 648402

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.0985

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0953

Gnomad4 NFE exome AF: 0.0868

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.135 AC: 20550 AN: 152002 Hom.: 1668 Cov.: 31 AF XY: 0.137 AC XY: 10201 AN XY: 74286

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.117

Alfa AF: 0.105 Hom.: 321

Bravo AF: 0.138

Asia WGS AF: 0.242 AC: 839 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	0.26
DANN	Benign	0.46
BranchPoint Hunter		1.0

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: rs7976407; hg19: chr12-113568797; COSMIC: COSV55658320;