chr1-178349970-G-A

Variant names:

• chr1-178349970-G-A
• rs2175254
• NM_170692.4:c.458-40130G>A

Variant summary

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

The NM_170692.4(RASAL2):​c.458-40130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 152,128 control chromosomes in the GnomAD database, including 550 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 0.079 (550 hom., cov: 31)
• Consequence: RASAL2 NM_170692.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

RASAL2 (HGNC:9874): (RAS protein activator like 2) This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASAL2	NM_170692.4	c.458-40130G>A		intron_variant	Intron 3 of 17	ENST00000367649.8	NP_733793.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASAL2	ENST00000367649.8	c.458-40130G>A		intron_variant	Intron 3 of 17	1	NM_170692.4	ENSP00000356621.3
RASAL2	ENST00000462775.5	c.13+8362G>A		intron_variant	Intron 1 of 15	1		ENSP00000420558.1
RASAL2	ENST00000696605.1	c.845-40130G>A		intron_variant	Intron 3 of 17			ENSP00000512749.1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12041 AN: 152012 Hom.: 551 Cov.: 31

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0677

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0863

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

GnomAD4 genome AF: 0.0791 AC: 12039 AN: 152128 Hom.: 550 Cov.: 31 AF XY: 0.0762 AC XY: 5666 AN XY: 74372

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0984 Hom.: 716

Bravo AF: 0.0810

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.50
DANN	Benign	0.61

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: rs2175254; hg19: chr1-178319105;