dbSNP rs7768897: AMD1:c.427+724A>G (chr6-110891080-A-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_001634.6(AMD1):c.427+724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,232 control chromosomes in the GnomAD database, including 56,911 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 0.86 ( 56907 hom., cov: 32)

Exomes 𝑓: 0.90 ( 4 hom. )

Consequence

AMD1
NM_001634.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.523

Publications

9 publications found

Variant links:

Genes affected

AMD1 (HGNC:457): (adenosylmethionine decarboxylase 1) This gene encodes an important intermediate enzyme in polyamine biosynthesis. The polyamines spermine, spermidine, and putrescine are low-molecular-weight aliphatic amines essential for cellular proliferation and tumor promotion. Multiple alternatively spliced transcript variants have been identified. Pseudogenes of this gene are found on chromosomes 5, 6, 10, X and Y. [provided by RefSeq, Dec 2013]

AMD1 links:

ENSG00000298809 (HGNC:):

ENSG00000298809 links:

Genome browser will be placed here

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=-0.96).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMD1	NM_001634.6 link	c.427+724A>G		intron_variant	Intron 4 of 8	ENST00000368885.8	NP_001625.2	P17707-1B4DZ60Q6N0B2A0A088AWN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMD1	ENST00000368885.8 link	c.427+724A>G		intron_variant	Intron 4 of 8	1	NM_001634.6	ENSP00000357880.3		P17707-1

Frequencies

GnomAD3 genomes

AF:

0.863

AC:

131327

AN:

152104

Hom.:

56864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.912

Gnomad ASJ

AF:

0.943

Gnomad EAS

AF:

0.671

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.953

Gnomad NFE

AF:

0.875

Gnomad OTH

AF:

0.881

GnomAD4 exome

AF:

0.900

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.863

AC:

131429

AN:

152222

Hom.:

56907

Cov.:

AF XY:

0.858

AC XY:

63833

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.870

AC:

36118

AN:

41526

American (AMR)

AF:

0.912

AC:

13962

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.943

AC:

3275

AN:

3472

East Asian (EAS)

AF:

0.671

AC:

3471

AN:

5174

South Asian (SAS)

AF:

0.749

AC:

3616

AN:

4826

European-Finnish (FIN)

AF:

0.800

AC:

8471

AN:

10590

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.875

AC:

59519

AN:

68010

Other (OTH)

AF:

0.881

AC:

1862

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

934

1869

2803

3738

4672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.880

Hom.:

100819

Bravo

AF:

0.877

Asia WGS

AF:

0.726

AC:

2525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.46

(source)

DANN

Benign

0.47

PhyloP100

-0.52

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