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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001634.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMD1	NM_001634.6	MANE Select	c.427+724A>G	intron	N/A	NP_001625.2	P17707-1
AMD1	NM_001287214.1		c.340+724A>G	intron	N/A	NP_001274143.1	A0A088AWN0
AMD1	NM_001287215.2		c.220+724A>G	intron	N/A	NP_001274144.1	Q5VXN5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMD1	ENST00000368885.8	TSL:1 MANE Select	c.427+724A>G	intron	N/A	ENSP00000357880.3	P17707-1
AMD1	ENST00000451850.6	TSL:1	n.111-1081A>G	intron	N/A	ENSP00000389988.3	F6R5I9
AMD1	ENST00000612642.4	TSL:1	n.2071+724A>G	intron	N/A

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), 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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over