chr7-129283976-C-T

Variant names:

• chr7-129283976-C-T
• rs2056694
• NM_015328.4:c.363+58537C>T

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+58537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,044 control chromosomes in the GnomAD database, including 4,714 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 0.25 (4714 hom., cov: 32)
• Consequence: AHCYL2 NM_015328.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015328.4. 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
	AHCYL2	NM_015328.4	MANE Select	c.363+58537C>T		intron	N/A	NP_056143.1
	AHCYL2	NM_001130720.3		c.363+58537C>T		intron	N/A	NP_001124192.1
	AHCYL2	NM_001393387.1		c.363+58537C>T		intron	N/A	NP_001380316.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCYL2	ENST00000325006.8	TSL:1 MANE Select	c.363+58537C>T		intron	N/A	ENSP00000315931.3
	AHCYL2	ENST00000446544.6	TSL:1	c.363+58537C>T		intron	N/A	ENSP00000413639.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37577 AN: 151926 Hom.: 4707 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.247 AC: 37598 AN: 152044 Hom.: 4714 Cov.: 32 AF XY: 0.247 AC XY: 18333 AN XY: 74330

African (AFR) AF: 0.224 AC: 9273 AN: 41468

American (AMR) AF: 0.287 AC: 4381 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1671 AN: 5174

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1950 AN: 10568

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16665 AN: 67966

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.236 Hom.: 708

Bravo AF: 0.253

Asia WGS AF: 0.337 AC: 1168 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.33
PhyloP100		-0.21
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: rs2056694; hg19: chr7-128923817;