rs11979476

Positions:

• chr7-129353915-T-G

Variant summary

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

The NM_015328.4(AHCYL2):​c.364-25723T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,316 control chromosomes in the GnomAD database, including 5,384 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 0.27 (5384 hom., cov: 29)
• Consequence: AHCYL2 NM_015328.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHCYL2	NM_015328.4	c.364-25723T>G		intron_variant		ENST00000325006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHCYL2	ENST00000325006.8	c.364-25723T>G		intron_variant		1	NM_015328.4
AHCYL2	ENST00000446544.6	c.364-25726T>G		intron_variant		1
AHCYL2	ENST00000461161.5	n.159+2254T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40169 AN: 151198 Hom.: 5375 Cov.: 29

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.266 AC: 40207 AN: 151316 Hom.: 5384 Cov.: 29 AF XY: 0.264 AC XY: 19518 AN XY: 73882

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.270

Alfa AF: 0.253 Hom.: 2904

Bravo AF: 0.274

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.91

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: rs11979476; hg19: chr7-128993756;