Genetic Variant ENST00000265154.6:c.*527A>T (chr4-105631576-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000265154.6(ARHGEF38):c.*527A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 985,028 control chromosomes in the GnomAD database, including 33,058 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 0.32 ( 11123 hom., cov: 32)

Exomes 𝑓: 0.22 ( 21935 hom. )

Consequence

ARHGEF38
ENST00000265154.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

5 publications found

Variant links:

Genes affected

ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF38 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ARHGEF38 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF38	NM_001242729.2 link	c.656+531A>T		intron_variant	Intron 4 of 13	ENST00000420470.3	NP_001229658.1	Q9NXL2-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGEF38	ENST00000265154.6 link	c.*527A>T	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000265154.2	Q9NXL2-1
ARHGEF38	ENST00000420470.3 link	c.656+531A>T	intron_variant	Intron 4 of 13	5	NM_001242729.2	ENSP00000416125.2	Q9NXL2-2
ARHGEF38	ENST00000506828.1 link	n.382-13612A>T	intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48915

AN:

151954

Hom.:

11088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.219

AC:

182277

AN:

832956

Hom.:

21935

Cov.:

AF XY:

0.218

AC XY:

83831

AN XY:

384652

show subpopulations

African (AFR)

AF:

0.678

AC:

10705

AN:

15778

American (AMR)

AF:

0.255

AC:

251

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1660

AN:

5152

East Asian (EAS)

AF:

0.0972

AC:

353

AN:

3630

South Asian (SAS)

AF:

0.154

AC:

2530

AN:

16458

European-Finnish (FIN)

AF:

0.129

AC:

AN:

280

Middle Eastern (MID)

AF:

0.297

AC:

481

AN:

1618

European-Non Finnish (NFE)

AF:

0.210

AC:

160068

AN:

761766

Other (OTH)

AF:

0.227

AC:

6193

AN:

27290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

7109

14218

21326

28435

35544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7710

15420

23130

30840

38550

<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:

0.322

AC:

48996

AN:

152072

Hom.:

11123

Cov.:

AF XY:

0.313

AC XY:

23249

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.639

AC:

26474

AN:

41420

American (AMR)

AF:

0.282

AC:

4315

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1076

AN:

3468

East Asian (EAS)

AF:

0.101

AC:

525

AN:

5178

South Asian (SAS)

AF:

0.135

AC:

651

AN:

4818

European-Finnish (FIN)

AF:

0.0924

AC:

980

AN:

10608

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13885

AN:

67980

Other (OTH)

AF:

0.335

AC:

706

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1377

2753

4130

5506

6883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.263

Hom.:

945

Bravo

AF:

0.353

Asia WGS

AF:

0.160

AC:

557

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

0.44

(source)

DANN

Benign

0.65

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over