rs2142450

Variant names:

• chr21-14963081-C-T
• rs2142450
• NM_003489.4:c.*1635G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003489.4(NRIP1):​c.*1635G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,148 control chromosomes in the GnomAD database, including 2,334 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 (2330 hom., cov: 32)
  • Exomes 𝑓: 0.22 (4 hom.)
• Consequence: NRIP1 NM_003489.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

Genes affected

NRIP1 (HGNC:8001): (nuclear receptor interacting protein 1) Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein modulates transcriptional activity of the estrogen receptor. [provided by RefSeq, Jul 2008]

ENSG00000235609 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRIP1	NM_003489.4	c.*1635G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000318948.7	NP_003480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRIP1	ENST00000318948	c.*1635G>A		3_prime_UTR_variant	Exon 4 of 4	2	NM_003489.4	ENSP00000327213.4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24924 AN: 151886 Hom.: 2330 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.215 AC: 31 AN: 144 Hom.: 4 Cov.: 0 AF XY: 0.195 AC XY: 16 AN XY: 82

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.164 AC: 24940 AN: 152004 Hom.: 2330 Cov.: 32 AF XY: 0.162 AC XY: 12015 AN XY: 74322

Gnomad4 AFR AF: 0.0953

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.175

Alfa AF: 0.199 Hom.: 2773

Bravo AF: 0.156

Asia WGS AF: 0.148 AC: 515 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs2142450; hg19: chr21-16335402;