rs303533

Variant names:

• chr10-88806107-T-A
• rs303533
• NM_001128215.1:c.148-2191T>A

Variant summary

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

The ENST00000404743.9(LIPM):​c.148-2191T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 423,084 control chromosomes in the GnomAD database, including 6,559 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 0.16 (2099 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4460 hom.)
• Consequence: LIPM ENST00000404743.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 1 publications found

Genes affected

LIPM (HGNC:23455): (lipase family member M) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404743.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPM	NM_001128215.1	MANE Select	c.148-2191T>A		intron	N/A	NP_001121687.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPM	ENST00000404743.9	TSL:1 MANE Select	c.148-2191T>A		intron	N/A	ENSP00000383901.3
	LIPM	ENST00000539337.2	TSL:2	c.27+102T>A		intron	N/A	ENSP00000440375.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23893 AN: 152084 Hom.: 2099 Cov.: 33

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.174 AC: 47104 AN: 270882 Hom.: 4460 AF XY: 0.168 AC XY: 25868 AN XY: 154294

African (AFR) AF: 0.100 AC: 759 AN: 7576

American (AMR) AF: 0.169 AC: 3896 AN: 23028

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 1182 AN: 8218

East Asian (EAS) AF: 0.0155 AC: 129 AN: 8342

South Asian (SAS) AF: 0.110 AC: 5843 AN: 53196

European-Finnish (FIN) AF: 0.200 AC: 2312 AN: 11542

Middle Eastern (MID) AF: 0.120 AC: 285 AN: 2378

European-Non Finnish (NFE) AF: 0.212 AC: 30450 AN: 143750

Other (OTH) AF: 0.175 AC: 2248 AN: 12852

GnomAD4 genome AF: 0.157 AC: 23893 AN: 152202 Hom.: 2099 Cov.: 33 AF XY: 0.154 AC XY: 11433 AN XY: 74412

African (AFR) AF: 0.0981 AC: 4074 AN: 41530

American (AMR) AF: 0.146 AC: 2234 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.0162 AC: 84 AN: 5188

South Asian (SAS) AF: 0.0962 AC: 464 AN: 4824

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14048 AN: 67980

Other (OTH) AF: 0.147 AC: 311 AN: 2114

Alfa AF: 0.180 Hom.: 310

Bravo AF: 0.153

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.22
PhyloP100		-0.21
PromoterAI		-0.029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs303533; hg19: chr10-90565864;