chr19-41888067-T-C

Variant names:

• chr19-41888067-T-C
• ENST00000378152.8:c.30T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_199002.2(ARHGEF1):​c.30T>C​(p.Pro10Pro) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGEF1 NM_199002.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.413
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-41888067-T-C is Benign according to our data. Variant chr19-41888067-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2697380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.413 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.-16T>C		5_prime_UTR	Exon 2 of 29	NP_004697.2
	ARHGEF1	NM_199002.2		c.30T>C	p.Pro10Pro	synonymous	Exon 2 of 29	NP_945353.1	Q92888-3
	ARHGEF1	NM_001396000.1		c.-16T>C		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.30T>C	p.Pro10Pro	synonymous	Exon 2 of 27	ENSP00000367394.3	Q92888-4
	ARHGEF1	ENST00000337665.8	TSL:1	c.30T>C	p.Pro10Pro	synonymous	Exon 2 of 29	ENSP00000337261.3	Q92888-3
	ARHGEF1	ENST00000354532.8	TSL:1 MANE Select	c.-16T>C		5_prime_UTR	Exon 2 of 29	ENSP00000346532.3	Q92888-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.8
DANN	Benign	0.72
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr19-42392138;