Genetic Variant GMIP:c.1560+73C>A (chr19-19635342-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000203556.9(GMIP):c.1560+73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,563,630 control chromosomes in the GnomAD database, including 6,512 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 0.11 ( 1035 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5477 hom. )

Consequence

GMIP
ENST00000203556.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203

Publications

30 publications found

Variant links:

Genes affected

GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GMIP 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000203556.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GMIP	NM_016573.4	MANE Select	c.1560+73C>A	intron	N/A	NP_057657.2
GMIP	NM_001288999.2		c.1482+73C>A	intron	N/A	NP_001275928.1
GMIP	NM_001288998.2		c.1473+73C>A	intron	N/A	NP_001275927.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GMIP	ENST00000203556.9	TSL:1 MANE Select	c.1560+73C>A	intron	N/A	ENSP00000203556.3
GMIP	ENST00000587238.5	TSL:1	c.1482+73C>A	intron	N/A	ENSP00000467054.1
GMIP	ENST00000593186.1	TSL:5	c.789+73C>A	intron	N/A	ENSP00000465108.1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16466

AN:

152070

Hom.:

1023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0527

Gnomad EAS

AF:

0.0573

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0749

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0792

Gnomad OTH

AF:

0.0940

GnomAD4 exome

AF:

0.0851

AC:

120151

AN:

1411442

Hom.:

5477

Cov.:

AF XY:

0.0849

AC XY:

59353

AN XY:

698988

show subpopulations

African (AFR)

AF:

0.173

AC:

5627

AN:

32564

American (AMR)

AF:

0.138

AC:

5876

AN:

42516

Ashkenazi Jewish (ASJ)

AF:

0.0597

AC:

1403

AN:

23500

East Asian (EAS)

AF:

0.0594

AC:

2334

AN:

39312

South Asian (SAS)

AF:

0.109

AC:

8760

AN:

80542

European-Finnish (FIN)

AF:

0.0765

AC:

3955

AN:

51690

Middle Eastern (MID)

AF:

0.0489

AC:

236

AN:

4822

European-Non Finnish (NFE)

AF:

0.0808

AC:

87110

AN:

1078196

Other (OTH)

AF:

0.0832

AC:

4850

AN:

58300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5901

11802

17704

23605

29506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3380

6760

10140

13520

16900

<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:

0.108

AC:

16505

AN:

152188

Hom.:

1035

Cov.:

AF XY:

0.109

AC XY:

8114

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.169

AC:

7017

AN:

41512

American (AMR)

AF:

0.124

AC:

1901

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0527

AC:

183

AN:

3470

East Asian (EAS)

AF:

0.0573

AC:

296

AN:

5170

South Asian (SAS)

AF:

0.121

AC:

584

AN:

4830

European-Finnish (FIN)

AF:

0.0749

AC:

795

AN:

10612

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0792

AC:

5389

AN:

68006

Other (OTH)

AF:

0.103

AC:

217

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

752

1503

2255

3006

3758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0870

Hom.:

1947

Bravo

AF:

0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.6

(source)

DANN

Benign

0.48

PhyloP100

0.20

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