rs864702

chr20-34283744-A-Gchr20-34283744-A-T

Variant summary

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

The NM_000687.4(AHCY):c.1167+1696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,230 control chromosomes in the GnomAD database, including 57,813 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 0.87 (57813 hom., cov: 32)
• Consequence: AHCY NM_000687.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

AHCY (HGNC:343): (adenosylhomocysteinase) S-adenosylhomocysteine hydrolase belongs to the adenosylhomocysteinase family. It catalyzes the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to adenosine (Ado) and L-homocysteine (Hcy). Thus, it regulates the intracellular S-adenosylhomocysteine (SAH) concentration thought to be important for transmethylation reactions. Deficiency in this protein is one of the different causes of hypermethioninemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHCY	NM_000687.4	c.1167+1696T>C		intron_variant		ENST00000217426.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHCY	ENST00000217426.7	c.1167+1696T>C		intron_variant		1	NM_000687.4	P1
	ENST00000609218.1	n.440-1966T>C		intron_variant, non_coding_transcript_variant		4
AHCY	ENST00000538132.1	c.1083+1696T>C		intron_variant		2
AHCY	ENST00000480653.5	n.1315+1696T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132468 AN: 152112 Hom.: 57764 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.871 AC: 132572 AN: 152230 Hom.: 57813 Cov.: 32 AF XY: 0.869 AC XY: 64686 AN XY: 74434

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.866

Alfa AF: 0.877 Hom.: 9463

Bravo AF: 0.875

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.3
Dann	Benign	0.67

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: rs864702; hg19: chr20-32871550;