rs7768897

Variant names:

• chr6-110891080-A-G
• rs7768897
• NM_001634.6:c.427+724A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-110891080-A-G
• chr6-110891080-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 9 publications found

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]

ENSG00000298809 (HGNC:):

ACMG classification

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMD1	ENST00000368885.8	TSL:1 MANE Select	c.427+724A>G		intron	N/A	ENSP00000357880.3
	AMD1	ENST00000451850.6	TSL:1	n.111-1081A>G		intron	N/A	ENSP00000389988.3
	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.: 32

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: 9 AN: 10 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.833 AC: 5 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ 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.

GnomAD4 genome AF: 0.863 AC: 131429 AN: 152222 Hom.: 56907 Cov.: 32 AF XY: 0.858 AC XY: 63833 AN XY: 74420

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

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
DANN	Benign	0.47
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7768897; hg19: chr6-111212283; COSMIC: COSV64388152; COSMIC: COSV64388152;