NM_003489.4:c.*1635G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ASMER1 (HGNC:53135): (adipocyte associated metabolic related lncRNA 1)

ENSG00000229047 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	ENST00000318948.7	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.207 AC: 29 AN: 140

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0953 AC: 3956 AN: 41516

American (AMR) AF: 0.129 AC: 1971 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.140 AC: 726 AN: 5184

South Asian (SAS) AF: 0.151 AC: 725 AN: 4814

European-Finnish (FIN) AF: 0.207 AC: 2186 AN: 10574

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14125 AN: 67870

Other (OTH) AF: 0.175 AC: 369 AN: 2108

Alfa AF: 0.197 Hom.: 3138

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
PhyloP100		-0.10
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: rs2142450; hg19: chr21-16335402;