Genetic Variant NM_003643.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM1	NM_003643.4 link	c.328+36G>A		intron_variant	Intron 3 of 5	ENST00000259803.8	NP_003634.2	Q9NP62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCM1	ENST00000259803.8 link	c.328+36G>A		intron_variant	Intron 3 of 5	1	NM_003643.4	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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over