6-55608496-A-G

Variant names:

• chr6-55608496-A-G
• rs11754509
• XM_047418902.1:c.13-66356T>C

Variant summary

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

The XM_047418902.1(HMGCLL1):​c.13-66356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,280 control chromosomes in the GnomAD database, including 420 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 0.057 (420 hom., cov: 32)
• Consequence: HMGCLL1 XM_047418902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 4 publications found

Genes affected

HMGCLL1 (HGNC:21359): (3-hydroxy-3-methylglutaryl-CoA lyase like 1) Enables hydroxymethylglutaryl-CoA lyase activity. Involved in ketone body biosynthetic process. Located in several cellular components, including cytosol; endoplasmic reticulum; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8632 AN: 152162 Hom.: 420 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0406

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0430

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

GnomAD4 genome AF: 0.0567 AC: 8634 AN: 152280 Hom.: 420 Cov.: 32 AF XY: 0.0580 AC XY: 4321 AN XY: 74446

African (AFR) AF: 0.0127 AC: 526 AN: 41576

American (AMR) AF: 0.0273 AC: 418 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1615 AN: 10598

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5417 AN: 68022

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0654 Hom.: 491

Bravo AF: 0.0446

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.18
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11754509; hg19: chr6-55473294;