rs864702

Variant names:

• chr20-34283744-A-G
• rs864702
• NM_000687.4:c.1167+1696T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-34283744-A-G
• chr20-34283744-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

AHCY Gene-Disease associations (from GenCC):

• hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000272945 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000687.4. 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
	AHCY	NM_000687.4	MANE Select	c.1167+1696T>C		intron	N/A	NP_000678.1
	AHCY	NM_001322086.2		c.1173+1696T>C		intron	N/A	NP_001309015.1
	AHCY	NM_001362750.2		c.1167+1696T>C		intron	N/A	NP_001349679.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCY	ENST00000217426.7	TSL:1 MANE Select	c.1167+1696T>C		intron	N/A	ENSP00000217426.2
	AHCY	ENST00000538132.1	TSL:2	c.1083+1696T>C		intron	N/A	ENSP00000442820.1
	AHCY	ENST00000480653.5	TSL:2	n.1315+1696T>C		intron	N/A

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

African (AFR) AF: 0.851 AC: 35337 AN: 41522

American (AMR) AF: 0.911 AC: 13928 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2843 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4055 AN: 5172

South Asian (SAS) AF: 0.798 AC: 3850 AN: 4824

European-Finnish (FIN) AF: 0.877 AC: 9303 AN: 10608

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60374 AN: 68022

Other (OTH) AF: 0.866 AC: 1830 AN: 2114

Alfa AF: 0.875 Hom.: 9730

Bravo AF: 0.875

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		-0.13
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: rs864702; hg19: chr20-32871550;