rs4110091

Variant names:

• chr7-129292908-A-G
• rs4110091
• NM_015328.4:c.363+67469A>G

Variant summary

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

The NM_015328.4(AHCYL2):​c.363+67469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,258 control chromosomes in the GnomAD database, including 1,850 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 0.14 (1850 hom., cov: 32)
• Consequence: AHCYL2 NM_015328.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 4 publications found

Genes affected

AHCYL2 (HGNC:22204): (adenosylhomocysteinase like 2) The protein encoded by this gene acts as a homotetramer and may be involved in the conversion of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHCYL2	NM_015328.4	c.363+67469A>G		intron_variant	Intron 1 of 16	ENST00000325006.8	NP_056143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHCYL2	ENST00000325006.8	c.363+67469A>G		intron_variant	Intron 1 of 16	1	NM_015328.4	ENSP00000315931.3
AHCYL2	ENST00000446544.6	c.363+67469A>G		intron_variant	Intron 1 of 16	1		ENSP00000413639.2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21543 AN: 152140 Hom.: 1850 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.141 AC: 21532 AN: 152258 Hom.: 1850 Cov.: 32 AF XY: 0.140 AC XY: 10411 AN XY: 74440

African (AFR) AF: 0.0412 AC: 1713 AN: 41572

American (AMR) AF: 0.128 AC: 1965 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3472

East Asian (EAS) AF: 0.153 AC: 793 AN: 5182

South Asian (SAS) AF: 0.237 AC: 1144 AN: 4824

European-Finnish (FIN) AF: 0.160 AC: 1701 AN: 10608

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12973 AN: 67990

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.180 Hom.: 4426

Bravo AF: 0.133

Asia WGS AF: 0.181 AC: 629 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		1.2
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: rs4110091; hg19: chr7-128932749;