Genetic Variant GCM1:c.328+36G>A (chr6-53134036-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003643.4(GCM1):c.328+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,596,416 control chromosomes in the GnomAD database, including 444,819 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 0.74 ( 42013 hom., cov: 32)

Exomes 𝑓: 0.75 ( 402806 hom. )

Consequence

GCM1
NM_003643.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

7 publications found

Variant links:

Genes affected

GCM1 (HGNC:4197): (glial cells missing transcription factor 1) This gene encodes a DNA-binding protein with a gcm-motif (glial cell missing motif). The encoded protein is a homolog of the Drosophila glial cells missing gene (gcm). This protein binds to the GCM-motif (A/G)CCCGCAT, a novel sequence among known targets of DNA-binding proteins. The N-terminal DNA-binding domain confers the unique DNA-binding activity of this protein. [provided by RefSeq, Jul 2008]

GCM1 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCM1	NM_003643.4	MANE Select	c.328+36G>A		intron	N/A	NP_003634.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCM1	ENST00000259803.8	TSL:1 MANE Select	c.328+36G>A		intron	N/A	ENSP00000259803.7	Q9NP62

Frequencies

GnomAD3 genomes

AF:

0.742

AC:

112827

AN:

152066

Hom.:

41973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.777

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.579

Gnomad SAS

AF:

0.720

Gnomad FIN

AF:

0.845

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.719

GnomAD2 exomes

AF:

0.745

AC:

174202

AN:

233750

AF XY:

0.744

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.720

Gnomad EAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.836

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.735

GnomAD4 exome

AF:

0.745

AC:

1076585

AN:

1444232

Hom.:

402806

Cov.:

AF XY:

0.746

AC XY:

534586

AN XY:

716812

show subpopulations

African (AFR)

AF:

0.724

AC:

24049

AN:

33218

American (AMR)

AF:

0.801

AC:

34575

AN:

43190

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

18646

AN:

25800

East Asian (EAS)

AF:

0.542

AC:

21289

AN:

39250

South Asian (SAS)

AF:

0.743

AC:

63432

AN:

85402

European-Finnish (FIN)

AF:

0.833

AC:

43827

AN:

52642

Middle Eastern (MID)

AF:

0.708

AC:

3970

AN:

5608

European-Non Finnish (NFE)

AF:

0.748

AC:

822847

AN:

1099366

Other (OTH)

AF:

0.735

AC:

43950

AN:

59756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13460

26921

40381

53842

67302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20094

40188

60282

80376

100470

<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:

0.742

AC:

112924

AN:

152184

Hom.:

42013

Cov.:

AF XY:

0.746

AC XY:

55471

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.723

AC:

30003

AN:

41508

American (AMR)

AF:

0.777

AC:

11898

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2494

AN:

3470

East Asian (EAS)

AF:

0.579

AC:

2989

AN:

5158

South Asian (SAS)

AF:

0.720

AC:

3467

AN:

4818

European-Finnish (FIN)

AF:

0.845

AC:

8972

AN:

10616

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.747

AC:

50798

AN:

67998

Other (OTH)

AF:

0.720

AC:

1520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1481

2962

4443

5924

7405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.737

Hom.:

8503

Bravo

AF:

0.735

Asia WGS

AF:

0.696

AC:

2422

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.71

PhyloP100

-0.0030

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