Genetic Variant NM_001282290.2:c.658-2342C>T (chr17-45408425-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001282290.2(ARHGAP27):c.658-2342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,950 control chromosomes in the GnomAD database, including 9,346 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 0.35 ( 9344 hom., cov: 31)

Exomes 𝑓: 0.44 ( 2 hom. )

Consequence

ARHGAP27
NM_001282290.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.121

Publications

15 publications found

Variant links:

Genes affected

ARHGAP27 (HGNC:31813): (Rho GTPase activating protein 27) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may pay a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2013]

ARHGAP27 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282290.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP27	NM_001282290.2	MANE Select	c.658-2342C>T	intron	N/A	NP_001269219.1	Q6ZUM4-1
ARHGAP27	NM_001385384.1		c.658-2342C>T	intron	N/A	NP_001372313.1	E9PIR1
ARHGAP27	NM_001385385.1		c.57+1807C>T	intron	N/A	NP_001372314.1	A0A8I5KVA8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARHGAP27	ENST00000685559.1	MANE Select	c.658-2342C>T	intron	N/A	ENSP00000509127.1	Q6ZUM4-1
ARHGAP27	ENST00000868964.1		c.658-2342C>T	intron	N/A	ENSP00000539023.1
ARHGAP27	ENST00000868965.1		c.658-2342C>T	intron	N/A	ENSP00000539024.1

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52403

AN:

151816

Hom.:

9332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.367

GnomAD4 exome

AF:

0.438

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.600

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.345

AC:

52459

AN:

151934

Hom.:

9344

Cov.:

AF XY:

0.349

AC XY:

25955

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.382

AC:

15813

AN:

41440

American (AMR)

AF:

0.356

AC:

5432

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

1229

AN:

3464

East Asian (EAS)

AF:

0.544

AC:

2807

AN:

5156

South Asian (SAS)

AF:

0.368

AC:

1768

AN:

4808

European-Finnish (FIN)

AF:

0.337

AC:

3556

AN:

10562

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.306

AC:

20751

AN:

67922

Other (OTH)

AF:

0.366

AC:

772

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1725

3450

5174

6899

8624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.319

Hom.:

13697

Bravo

AF:

0.352

Asia WGS

AF:

0.458

AC:

1588

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.40

(source)

DANN

Benign

0.24

PhyloP100

-0.12

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over