rs538307

Variant names:

• chr4-81802721-G-A
• rs538307
• ENST00000638048.1:c.171+21797C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-81802721-G-A
• chr4-81802721-G-T

Variant summary

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

The ENST00000514050.6(RASGEF1B):​c.171+21797C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,104 control chromosomes in the GnomAD database, including 48,620 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 0.80 (48619 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: RASGEF1B ENST00000514050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.839 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.171+21797C>T		intron_variant	Intron 3 of 16	5		ENSP00000490436.1
RASGEF1B	ENST00000514050.6	c.171+21797C>T		intron_variant	Intron 3 of 3	2		ENSP00000490814.1
RASGEF1B	ENST00000508294.1	n.429+86C>T		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121379 AN: 151984 Hom.: 48566 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.801

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AC XY: 0 AN XY: 0

Gnomad4 AFR exome AF: 1.00

GnomAD4 genome AF: 0.799 AC: 121492 AN: 152102 Hom.: 48619 Cov.: 32 AF XY: 0.799 AC XY: 59442 AN XY: 74356

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.801

Alfa AF: 0.790 Hom.: 5545

Bravo AF: 0.805

Asia WGS AF: 0.814 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs538307; hg19: chr4-82723874;