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. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638048.1(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 ENST00000638048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.846 AC: 35124 AN: 41518

American (AMR) AF: 0.811 AC: 12392 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2673 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3773 AN: 5148

South Asian (SAS) AF: 0.858 AC: 4135 AN: 4822

European-Finnish (FIN) AF: 0.766 AC: 8103 AN: 10574

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52651 AN: 67968

Other (OTH) AF: 0.801 AC: 1692 AN: 2112

Alfa AF: 0.792 Hom.: 5820

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
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs538307; hg19: chr4-82723874;