dbSNP rs77865386: NRROS:c.*266A>G (chr3-196661988-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_198565.3(NRROS):c.*266A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 329,630 control chromosomes in the GnomAD database, including 36 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 0.011 ( 31 hom., cov: 28)

Exomes 𝑓: 0.0017 ( 5 hom. )

Consequence

NRROS
NM_198565.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

NRROS (HGNC:24613): (negative regulator of reactive oxygen species) Enables transforming growth factor beta binding activity. Predicted to be involved in several processes, including microglia development; sequestering of TGFbeta in extracellular matrix; and transforming growth factor beta1 activation. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

NRROS links:

PIGX (HGNC:26046): (phosphatidylinositol glycan anchor biosynthesis class X) This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

PIGX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1546/147198) while in subpopulation AFR AF= 0.0377 (1498/39752). AF 95% confidence interval is 0.0361. There are 31 homozygotes in gnomad4. There are 699 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRROS	NM_198565.3 link	c.*266A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000328557.5	NP_940967.1	Q86YC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRROS	ENST00000328557.5 link	c.*266A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_198565.3	ENSP00000328625.4		Q86YC3
PIGX	ENST00000426755.5 link	c.-12+7341A>G		intron_variant	Intron 2 of 5	3		ENSP00000409073.1		C9JLT7

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1541

AN:

147084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00230

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000743

Gnomad OTH

AF:

0.00543

GnomAD4 exome

AF:

0.00168

AC:

307

AN:

182432

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

139

AN XY:

92982

show subpopulations

Gnomad4 AFR exome

AF:

0.0425

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00183

GnomAD4 genome

AF:

0.0105

AC:

1546

AN:

147198

Hom.:

Cov.:

AF XY:

0.00976

AC XY:

699

AN XY:

71596

show subpopulations

Gnomad4 AFR

AF:

0.0377

Gnomad4 AMR

AF:

0.00230

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000743

Gnomad4 OTH

AF:

0.00538

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.86

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over