NM_004706.4:c.-17C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004706.4(ARHGEF1):c.-17C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,612,660 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 6 hom. )

Consequence

ARHGEF1
NM_004706.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.505

Publications

1 publications found

Variant links:

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

ARHGEF1 links:

ENSG00000296972 (HGNC:):

ENSG00000296972 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004104078).

BP6

Variant 19-41888066-C-T is Benign according to our data. Variant chr19-41888066-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1050715.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004706.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGEF1	NM_004706.4	MANE Select	c.-17C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 29	NP_004697.2
ARHGEF1	NM_004706.4	MANE Select	c.-17C>T	splice_region	Exon 2 of 29	NP_004697.2
ARHGEF1	NM_004706.4	MANE Select	c.-17C>T	5_prime_UTR	Exon 2 of 29	NP_004697.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGEF1	ENST00000354532.8	TSL:1 MANE Select	c.-17C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 29	ENSP00000346532.3	Q92888-1
ARHGEF1	ENST00000347545.8	TSL:1	c.-17C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 28	ENSP00000344429.3	Q92888-2
ARHGEF1	ENST00000354532.8	TSL:1 MANE Select	c.-17C>T	splice_region	Exon 2 of 29	ENSP00000346532.3	Q92888-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000560

AC:

140

AN:

249838

AF XY:

0.000785

show subpopulations

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000270

AC:

395

AN:

1460354

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

281

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00426

AC:

367

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4930

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111762

Other (OTH)

AF:

0.000232

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.413

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000190

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00601

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000520

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.77

PhyloP100

0.51

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.8

REVEL

Benign

0.087

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

0.83

Vest4

0.27

MutPred

0.17

Loss of helix (P = 0.0237)

MVP

0.48

MPC

0.44

ClinPred

0.14

GERP RS

2.7

gMVP

0.18

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over