19-41888082-G-A

Variant names:

• chr19-41888082-G-A
• rs1555845520
• ENST00000378152.8:c.45G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_199002.2(ARHGEF1):​c.45G>A​(p.Glu15Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ARHGEF1 NM_199002.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

ARHGEF1 (HGNC:681): (Rho guanine nucleotide exchange factor 1) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

ARHGEF1 Gene-Disease associations (from GenCC):

• immunodeficiency 62

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000296972 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199002.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF1	NM_004706.4	MANE Select	c.-1G>A		5_prime_UTR	Exon 2 of 29	NP_004697.2
	ARHGEF1	NM_199002.2		c.45G>A	p.Glu15Glu	synonymous	Exon 2 of 29	NP_945353.1	Q92888-3
	ARHGEF1	NM_001396000.1		c.-1G>A		5_prime_UTR	Exon 2 of 30	NP_001382929.1	M0QZR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF1	ENST00000378152.8	TSL:1	c.45G>A	p.Glu15Glu	synonymous	Exon 2 of 27	ENSP00000367394.3	Q92888-4
	ARHGEF1	ENST00000337665.8	TSL:1	c.45G>A	p.Glu15Glu	synonymous	Exon 2 of 29	ENSP00000337261.3	Q92888-3
	ARHGEF1	ENST00000354532.8	TSL:1 MANE Select	c.-1G>A		5_prime_UTR	Exon 2 of 29	ENSP00000346532.3	Q92888-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250614 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs1555845520; hg19: chr19-42392153;