6-55608496-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGCLL1	XM_047418902.1	c.13-66356T>C		intron_variant	Intron 1 of 8		XP_047274858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0714 Hom.: 332

Bravo AF: 0.0446

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11754509; hg19: chr6-55473294;