rs6869328

Positions:

• chr5-81085345-A-C
• chr5-81085345-A-G

Variant summary

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

The NM_006909.3(RASGRF2):​c.1162-457A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,242 control chromosomes in the GnomAD database, including 772 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 0.093 (772 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.1162-457A>C		intron_variant		ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.1162-457A>C		intron_variant		1	NM_006909.3	ENSP00000265080	P1
RASGRF2	ENST00000503795.1	c.1162-457A>C		intron_variant, NMD_transcript_variant		1		ENSP00000421771
RASGRF2	ENST00000638442.1	c.1162-457A>C		intron_variant		5		ENSP00000491428
RASGRF2	ENST00000502677.1	n.1087-457A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14197 AN: 152124 Hom.: 766 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0935 AC: 14234 AN: 152242 Hom.: 772 Cov.: 32 AF XY: 0.0928 AC XY: 6912 AN XY: 74454

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.0899

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0720 Hom.: 285

Bravo AF: 0.0964

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.87

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: rs6869328; hg19: chr5-80381164;