rs320771

Variant names:

• chr4-81968245-T-C
• rs320771
• ENST00000638048.1:c.70-52887A>G

Variant summary

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

The ENST00000514050.6(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 ENST00000514050.6 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1B	ENST00000638048.1	c.70-52887A>G		intron_variant	Intron 1 of 16	5		ENSP00000490436.1
RASGEF1B	ENST00000514050.6	c.70-52887A>G		intron_variant	Intron 1 of 3	2		ENSP00000490814.1
RASGEF1B	ENST00000508294.1	n.245-52887A>G		intron_variant	Intron 1 of 4	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;