rs7553933

Positions:

• chr1-110000463-T-C

Variant summary

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

The NM_006621.7(AHCYL1):​c.121-8571T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,224 control chromosomes in the GnomAD database, including 2,989 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 0.11 (2989 hom., cov: 32)
• Consequence: AHCYL1 NM_006621.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

AHCYL1 (HGNC:344): (adenosylhomocysteinase like 1) The protein encoded by this gene interacts with inositol 1,4,5-trisphosphate receptor, type 1 and may be involved in the conversion of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. Several transcript variants encoding two 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL1	NM_006621.7	c.121-8571T>C		intron_variant		ENST00000369799.10	NP_006612.2
AHCYL1	NM_001242673.2	c.-21-8571T>C		intron_variant			NP_001229602.1
AHCYL1	XM_011540535.3	c.121-8571T>C		intron_variant			XP_011538837.1
AHCYL1	XM_047440112.1	c.121-8571T>C		intron_variant			XP_047296068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL1	ENST00000369799.10	c.121-8571T>C		intron_variant		1	NM_006621.7	ENSP00000358814	P1
AHCYL1	ENST00000393614.8	c.-21-8571T>C		intron_variant		2		ENSP00000377238
AHCYL1	ENST00000475081.1	n.159-8571T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17263 AN: 152106 Hom.: 2971 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0455

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.114 AC: 17317 AN: 152224 Hom.: 2989 Cov.: 32 AF XY: 0.110 AC XY: 8169 AN XY: 74458

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.0435

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0418 Hom.: 344

Bravo AF: 0.128

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.2
DANN	Benign	0.58

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: rs7553933; hg19: chr1-110543085;