Genetic Variant GCM1:c.328+14A>C (chr6-53134058-T-G) – 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+14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,608,394 control chromosomes in the GnomAD database, including 423,696 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 0.68 ( 36061 hom., cov: 32)

Exomes 𝑓: 0.73 ( 387635 hom. )

Consequence

GCM1
NM_003643.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCM1	NM_003643.4 link	c.328+14A>C		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+14A>C		intron_variant	Intron 3 of 5	1	NM_003643.4	ENSP00000259803.7		Q9NP62

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103814

AN:

151994

Hom.:

36028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.553

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.579

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.835

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.662

GnomAD2 exomes

AF:

0.721

AC:

178044

AN:

246840

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.549

Gnomad AMR exome

AF:

0.786

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.568

Gnomad FIN exome

AF:

0.827

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.715

GnomAD4 exome

AF:

0.728

AC:

1059730

AN:

1456282

Hom.:

387635

Cov.:

AF XY:

0.729

AC XY:

527148

AN XY:

723514

show subpopulations

African (AFR)

AF:

0.551

AC:

18392

AN:

33400

American (AMR)

AF:

0.781

AC:

34722

AN:

44468

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

17440

AN:

26094

East Asian (EAS)

AF:

0.542

AC:

21447

AN:

39558

South Asian (SAS)

AF:

0.736

AC:

63415

AN:

86146

European-Finnish (FIN)

AF:

0.824

AC:

43872

AN:

53236

Middle Eastern (MID)

AF:

0.682

AC:

3905

AN:

5730

European-Non Finnish (NFE)

AF:

0.735

AC:

813791

AN:

1107472

Other (OTH)

AF:

0.710

AC:

42746

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

15065

30130

45196

60261

75326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20032

40064

60096

80128

100160

<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:

0.683

AC:

103897

AN:

152112

Hom.:

36061

Cov.:

AF XY:

0.688

AC XY:

51178

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.553

AC:

22935

AN:

41470

American (AMR)

AF:

0.740

AC:

11325

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2279

AN:

3466

East Asian (EAS)

AF:

0.580

AC:

2993

AN:

5160

South Asian (SAS)

AF:

0.715

AC:

3448

AN:

4824

European-Finnish (FIN)

AF:

0.835

AC:

8846

AN:

10596

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.734

AC:

49912

AN:

67994

Other (OTH)

AF:

0.664

AC:

1400

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1666

3332

4999

6665

8331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.655

Hom.:

4956

Bravo

AF:

0.669

Asia WGS

AF:

0.684

AC:

2380

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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