chr21-15052546-G-T

Variant names:

• chr21-15052546-G-T
• rs1041404
• NM_003489.4:c.-537-8972C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003489.4(NRIP1):​c.-537-8972C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>A		intron	N/A	NP_003480.2
	NRIP1	NM_001439275.1		c.-971-8972C>A		intron	N/A	NP_001426204.1
	NRIP1	NM_001439276.1		c.-520-8972C>A		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>A		intron	N/A	ENSP00000327213.4
	NRIP1	ENST00000638122.1	TSL:1	c.-414-8972C>A		intron	N/A	ENSP00000490103.1
	NRIP1	ENST00000400199.5	TSL:3	c.-414-8972C>A		intron	N/A	ENSP00000383060.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.019
DANN	Benign	0.34
PhyloP100		-1.3

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;