21-15052546-G-A

Variant names:

• chr21-15052546-G-A
• rs1041404
• NM_003489.4:c.-537-8972C>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.-537-8972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,936 control chromosomes in the GnomAD database, including 11,892 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 0.37 (11892 hom., cov: 32)
• Consequence: NRIP1 NM_003489.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 4 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)

ENSG00000279390 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRIP1	NM_003489.4	MANE Select	c.-537-8972C>T		intron	N/A	NP_003480.2
	NRIP1	NM_001439275.1		c.-971-8972C>T		intron	N/A	NP_001426204.1
	NRIP1	NM_001439276.1		c.-520-8972C>T		intron	N/A	NP_001426205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRIP1	ENST00000318948.7	TSL:2 MANE Select	c.-537-8972C>T		intron	N/A	ENSP00000327213.4
	NRIP1	ENST00000638122.1	TSL:1	c.-414-8972C>T		intron	N/A	ENSP00000490103.1
	NRIP1	ENST00000400199.5	TSL:3	c.-414-8972C>T		intron	N/A	ENSP00000383060.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55578 AN: 151814 Hom.: 11862 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.366 AC: 55664 AN: 151936 Hom.: 11892 Cov.: 32 AF XY: 0.363 AC XY: 26928 AN XY: 74260

African (AFR) AF: 0.603 AC: 24966 AN: 41392

American (AMR) AF: 0.336 AC: 5137 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1778 AN: 5176

South Asian (SAS) AF: 0.255 AC: 1228 AN: 4816

European-Finnish (FIN) AF: 0.240 AC: 2529 AN: 10540

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18002 AN: 67954

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.274 Hom.: 1773

Bravo AF: 0.387

Asia WGS AF: 0.319 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.42
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1041404; hg19: chr21-16424867;