rs2776043

Variant names:

• chr21-14984720-C-T
• rs2776043
• NM_003489.4:c.-334-16194G>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.-334-16194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,048 control chromosomes in the GnomAD database, including 3,204 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 0.20 (3204 hom., cov: 32)
• Consequence: NRIP1 NM_003489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRIP1	NM_003489.4	c.-334-16194G>A		intron_variant	Intron 3 of 3	ENST00000318948.7	NP_003480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRIP1	ENST00000318948.7	c.-334-16194G>A		intron_variant	Intron 3 of 3	2	NM_003489.4	ENSP00000327213.4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29880 AN: 151930 Hom.: 3201 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.197 AC: 29896 AN: 152048 Hom.: 3204 Cov.: 32 AF XY: 0.194 AC XY: 14451 AN XY: 74320

African (AFR) AF: 0.136 AC: 5660 AN: 41484

American (AMR) AF: 0.148 AC: 2259 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3466

East Asian (EAS) AF: 0.142 AC: 735 AN: 5176

South Asian (SAS) AF: 0.127 AC: 610 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2626 AN: 10558

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16555 AN: 67956

Other (OTH) AF: 0.191 AC: 403 AN: 2114

Alfa AF: 0.205 Hom.: 551

Bravo AF: 0.188

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.56
PhyloP100		-0.39
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: rs2776043; hg19: chr21-16357041;