Genetic Variant ARHGAP44:c.387+1318G>C (chr17-12917329-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014859.6(ARHGAP44):c.387+1318G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 153,760 control chromosomes in the GnomAD database, including 6,805 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 0.23 ( 6790 hom., cov: 32)

Exomes 𝑓: 0.11 ( 15 hom. )

Consequence

ARHGAP44
NM_014859.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.379

Publications

13 publications found

Variant links:

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP44 links:

MIR1269B (HGNC:41787): (microRNA 1269b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR1269B links:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6 link	c.387+1318G>C		intron_variant	Intron 5 of 20	ENST00000379672.10	NP_055674.4	Q17R89-1Q69Z00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10 link	c.387+1318G>C		intron_variant	Intron 5 of 20	1	NM_014859.6	ENSP00000368994.5		Q17R89-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34243

AN:

151984

Hom.:

6769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0830

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0733

Gnomad OTH

AF:

0.183

GnomAD2 exomes

AF:

0.0824

AC:

AN:

364

AF XY:

0.0750

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad EAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.0833

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.107

AC:

178

AN:

1658

Hom.:

Cov.:

AF XY:

0.109

AC XY:

103

AN XY:

948

show subpopulations

African (AFR)

AF:

0.367

AC:

AN:

American (AMR)

AF:

0.286

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.273

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0920

AC:

AN:

772

European-Non Finnish (NFE)

AF:

0.0639

AC:

AN:

610

Other (OTH)

AF:

0.162

AC:

AN:

130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

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:

0.226

AC:

34305

AN:

152102

Hom.:

6790

Cov.:

AF XY:

0.227

AC XY:

16865

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.517

AC:

21424

AN:

41468

American (AMR)

AF:

0.156

AC:

2382

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.431

AC:

2218

AN:

5146

South Asian (SAS)

AF:

0.296

AC:

1424

AN:

4818

European-Finnish (FIN)

AF:

0.0830

AC:

878

AN:

10584

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0733

AC:

4983

AN:

68020

Other (OTH)

AF:

0.184

AC:

387

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1065

2131

3196

4262

5327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.142

Hom.:

425

Bravo

AF:

0.241

Asia WGS

AF:

0.353

AC:

1226

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.93

(source)

DANN

Benign

0.54

PhyloP100

-0.38

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