rs320771

chr4-81968245-T-C

Variant summary

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

The ENST00000638048.1(RASGEF1B):c.70-52887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,046 control chromosomes in the GnomAD database, including 4,065 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 0.22 (4065 hom., cov: 32)
• Consequence: RASGEF1B ENST00000638048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

RASGEF1B (HGNC:24881): (RasGEF domain family member 1B) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. Predicted to be located in early endosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1B	ENST00000514050.6	c.70-52887A>G		intron_variant		2
RASGEF1B	ENST00000638048.1	c.70-52887A>G		intron_variant		5
RASGEF1B	ENST00000512716.1	c.70-52887A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33800 AN: 151926 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.223 AC: 33839 AN: 152046 Hom.: 4065 Cov.: 32 AF XY: 0.221 AC XY: 16422 AN XY: 74326

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.234

Alfa AF: 0.226 Hom.: 592

Bravo AF: 0.221

Asia WGS AF: 0.196 AC: 682 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.48
Dann	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs320771; hg19: chr4-82889398;