rs4715555

Variant names:

• chr6-55583812-G-A
• rs4715555
• XM_047418902.1:c.13-41672C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-55583812-G-A
• chr6-55583812-G-C
• chr6-55583812-G-T

Variant summary

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

The XM_047418902.1(HMGCLL1):​c.13-41672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,972 control chromosomes in the GnomAD database, including 35,281 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 0.67 (35281 hom., cov: 32)
• Consequence: HMGCLL1 XM_047418902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGCLL1	XM_047418902.1	c.13-41672C>T		intron_variant	Intron 1 of 8		XP_047274858.1
HMGCLL1	XM_047418904.1	c.-190+23497C>T		intron_variant	Intron 1 of 8		XP_047274860.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102091 AN: 151854 Hom.: 35235 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.672 AC: 102197 AN: 151972 Hom.: 35281 Cov.: 32 AF XY: 0.680 AC XY: 50498 AN XY: 74300

African (AFR) AF: 0.805 AC: 33401 AN: 41482

American (AMR) AF: 0.636 AC: 9690 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2478 AN: 3462

East Asian (EAS) AF: 0.901 AC: 4654 AN: 5164

South Asian (SAS) AF: 0.782 AC: 3766 AN: 4818

European-Finnish (FIN) AF: 0.639 AC: 6759 AN: 10572

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39190 AN: 67928

Other (OTH) AF: 0.698 AC: 1469 AN: 2106

Alfa AF: 0.611 Hom.: 119063

Bravo AF: 0.678

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.57
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs4715555; hg19: chr6-55448610;