rs11202709

Variant names:

• chr10-88314248-A-G
• rs11202709
• NM_001031709.3:c.876+218T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-88314248-A-G
• chr10-88314248-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001031709.3(RNLS):​c.876+218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,140 control chromosomes in the GnomAD database, including 4,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4547 hom., cov: 32)
• Consequence: RNLS NM_001031709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108
• Publications: 4 publications found

Genes affected

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

LOC101929727 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-88314248-A-G is Benign according to our data. Variant chr10-88314248-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	NM_001031709.3	MANE Select	c.876+218T>C		intron	N/A	NP_001026879.2	Q5VYX0-1
	RNLS	NM_018363.4		c.876+218T>C		intron	N/A	NP_060833.1	Q5VYX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNLS	ENST00000331772.9	TSL:1 MANE Select	c.876+218T>C		intron	N/A	ENSP00000332530.4	Q5VYX0-1
	RNLS	ENST00000371947.7	TSL:2	c.876+218T>C		intron	N/A	ENSP00000361015.3	Q5VYX0-2

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34704 AN: 152022 Hom.: 4544 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.228 AC: 34721 AN: 152140 Hom.: 4547 Cov.: 32 AF XY: 0.233 AC XY: 17294 AN XY: 74362

African (AFR) AF: 0.108 AC: 4490 AN: 41534

American (AMR) AF: 0.255 AC: 3901 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.170 AC: 878 AN: 5178

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4816

European-Finnish (FIN) AF: 0.356 AC: 3765 AN: 10562

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18953 AN: 67988

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.254 Hom.: 1021

Bravo AF: 0.211

Asia WGS AF: 0.246 AC: 860 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.11
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: rs11202709; hg19: chr10-90074005;