Genetic Variant GUCD1:c.295-321G>T (chr22-24547326-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001284254.2(GUCD1):c.295-321G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 311,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

GUCD1
NM_001284254.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.272

Publications

4 publications found

Variant links:

Genes affected

GUCD1 (HGNC:14237): (guanylyl cyclase domain containing 1)

GUCD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GUCD1	NM_001284254.2	MANE Select	c.295-321G>T	intron	N/A	NP_001271183.1	Q96NT3-2
GUCD1	NM_001284251.2		c.463-321G>T	intron	N/A	NP_001271180.1	A0A087WVD9
GUCD1	NM_001284252.2		c.463-321G>T	intron	N/A	NP_001271181.1	Q96NT3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GUCD1	ENST00000435822.6	TSL:1 MANE Select	c.295-321G>T	intron	N/A	ENSP00000405985.1	Q96NT3-2
GUCD1	ENST00000621833.4	TSL:1	c.463-321G>T	intron	N/A	ENSP00000479370.1	A0A087WVD9
GUCD1	ENST00000404664.7	TSL:2	c.463-321G>T	intron	N/A	ENSP00000384121.3	Q96NT3-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

159782

Hom.:

Cov.:

AF XY:

0.0000708

AC XY:

AN XY:

84738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

5662

American (AMR)

AF:

0.00

AC:

AN:

7298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4768

East Asian (EAS)

AF:

0.00

AC:

AN:

9442

South Asian (SAS)

AF:

0.000346

AC:

AN:

20240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

634

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

95322

Other (OTH)

AF:

0.00

AC:

AN:

9054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

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:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74204

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

2470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

(source)

DANN

Benign

0.74

PhyloP100

-0.27

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