chr6-110891080-A-G

Position:

• chr6-110891080-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368885.8(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 ENST00000368885.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AMD1	NM_001634.6	c.427+724A>G		intron_variant		ENST00000368885.8	NP_001625.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMD1	ENST00000368885.8	c.427+724A>G		intron_variant		1	NM_001634.6	ENSP00000357880	P1

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

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

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

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.912

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.881

Alfa AF: 0.879 Hom.: 79497

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
DANN	Benign	0.47

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

LitVar

Other links and lift over

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