rs2822994

Positions:

• chr21-14988736-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRIP1	NM_003489.4	c.-334-20210C>T		intron_variant		ENST00000318948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRIP1	ENST00000318948.7	c.-334-20210C>T		intron_variant		2	NM_003489.4	P1
	ENST00000436429.1	n.204-3498G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.163

Alfa AF: 0.149 Hom.: 2432

Bravo AF: 0.161

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.7
DANN	Benign	0.40

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: rs2822994; hg19: chr21-16361057;