rs316274

Positions:

• chr1-178173073-G-A
• chr1-178173073-G-C

Variant summary

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

The NM_170692.4(RASAL2):​c.202+78379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,950 control chromosomes in the GnomAD database, including 6,225 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 0.26 (6225 hom., cov: 32)
• Consequence: RASAL2 NM_170692.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASAL2	NM_170692.4	c.202+78379G>A		intron_variant		ENST00000367649.8	NP_733793.2
RASAL2	XM_011510166.3	c.202+78379G>A		intron_variant			XP_011508468.1
RASAL2	XM_011510167.3	c.202+78379G>A		intron_variant			XP_011508469.1
RASAL2	XM_047434837.1	c.202+78379G>A		intron_variant			XP_047290793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASAL2	ENST00000367649.8	c.202+78379G>A		intron_variant		1	NM_170692.4	ENSP00000356621	P3
RASAL2	ENST00000465723.1	n.526+47572G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39846 AN: 151830 Hom.: 6228 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.262 AC: 39841 AN: 151950 Hom.: 6225 Cov.: 32 AF XY: 0.263 AC XY: 19569 AN XY: 74270

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.274

Alfa AF: 0.311 Hom.: 4747

Bravo AF: 0.243

Asia WGS AF: 0.221 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.78

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: rs316274; hg19: chr1-178142208;