rs2822994

Variant names:

• chr21-14988736-G-A
• rs2822994
• NM_003489.4:c.-334-20210C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003489.4(NRIP1):​c.-334-20210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,000 control chromosomes in the GnomAD database, including 2,005 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 (2005 hom., cov: 31)
• Consequence: NRIP1 NM_003489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910
• Publications: 5 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)

ENSG00000231201 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003489.4. 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
	NRIP1	NM_003489.4	MANE Select	c.-334-20210C>T		intron	N/A	NP_003480.2	P48552
	NRIP1	NM_001439275.1		c.-785-544C>T		intron	N/A	NP_001426204.1
	NRIP1	NM_001439276.1		c.-335+2465C>T		intron	N/A	NP_001426205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRIP1	ENST00000318948.7	TSL:2 MANE Select	c.-334-20210C>T		intron	N/A	ENSP00000327213.4	P48552
	NRIP1	ENST00000638122.1	TSL:1	c.-334-20210C>T		intron	N/A	ENSP00000490103.1	A0A1B0GUG9
	NRIP1	ENST00000400199.5	TSL:3	c.-334-20210C>T		intron	N/A	ENSP00000383060.1	P48552

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23641 AN: 151882 Hom.: 2005 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.156 AC: 23649 AN: 152000 Hom.: 2005 Cov.: 31 AF XY: 0.159 AC XY: 11848 AN XY: 74296

African (AFR) AF: 0.138 AC: 5738 AN: 41472

American (AMR) AF: 0.214 AC: 3262 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1646 AN: 5150

South Asian (SAS) AF: 0.192 AC: 927 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1222 AN: 10552

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9697 AN: 67976

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.149 Hom.: 3060

Bravo AF: 0.161

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.40
PhyloP100		0.91
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: rs2822994; hg19: chr21-16361057;