10-88583641-A-G

Variant names:

• chr10-88583641-A-G
• rs2576178
• ENST00000702048.2:n.735A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000702048.2(ENSG00000289952):​n.735A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 988,076 control chromosomes in the GnomAD database, including 38,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6699 hom., cov: 32)
  • Exomes 𝑓: 0.27 (31577 hom.)
• Consequence: ENSG00000289952 ENST00000702048.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.248
• Publications: 45 publications found

Genes affected

ENSG00000289952 (HGNC:):

LIPJ (HGNC:21773): (lipase family member J) Predicted to enable hydrolase activity, acting on ester bonds. Predicted to be involved in lipid catabolic process. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

RNLS (HGNC:25641): (renalase, FAD dependent amine oxidase) Enables several functions, including NADH binding activity; epinephrine binding activity; and monoamine oxidase activity. Involved in negative regulation of blood pressure and negative regulation of heart rate. Located in extracellular region. Implicated in essential hypertension and hypertension. Biomarker of end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

RNLS Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-88583641-A-G is Benign according to our data. Variant chr10-88583641-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000702048.2. 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
	LIPJ	NR_172141.1		n.735A>G		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289952	ENST00000702048.2		n.735A>G		non_coding_transcript_exon	Exon 1 of 1
	RNLS	ENST00000371947.7	TSL:2	c.-451T>C		5_prime_UTR	Exon 1 of 7	ENSP00000361015.3

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44022 AN: 152056 Hom.: 6689 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.274 AC: 228742 AN: 835902 Hom.: 31577 Cov.: 32 AF XY: 0.273 AC XY: 105436 AN XY: 386136

African (AFR) AF: 0.266 AC: 4224 AN: 15862

American (AMR) AF: 0.430 AC: 470 AN: 1094

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1762 AN: 5222

East Asian (EAS) AF: 0.537 AC: 1988 AN: 3704

South Asian (SAS) AF: 0.278 AC: 4661 AN: 16770

European-Finnish (FIN) AF: 0.250 AC: 96 AN: 384

Middle Eastern (MID) AF: 0.256 AC: 416 AN: 1626

European-Non Finnish (NFE) AF: 0.271 AC: 207205 AN: 763790

Other (OTH) AF: 0.289 AC: 7920 AN: 27450

GnomAD4 genome AF: 0.290 AC: 44056 AN: 152174 Hom.: 6699 Cov.: 32 AF XY: 0.292 AC XY: 21738 AN XY: 74428

African (AFR) AF: 0.268 AC: 11148 AN: 41524

American (AMR) AF: 0.362 AC: 5534 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.535 AC: 2767 AN: 5170

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4828

European-Finnish (FIN) AF: 0.242 AC: 2570 AN: 10598

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18620 AN: 67986

Other (OTH) AF: 0.305 AC: 644 AN: 2112

Alfa AF: 0.283 Hom.: 7659

Bravo AF: 0.297

Asia WGS AF: 0.425 AC: 1473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17216203)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.25
PromoterAI		-0.036	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2576178; hg19: chr10-90343398;