rs796052182

Variant names:

• chr21-14967553-T-A
• NM_003489.4:c.640A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-14967553-T-A
• chr21-14967553-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_003489.4(NRIP1):​c.640A>T​(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: NRIP1 NM_003489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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]

ENSG00000235609 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33004475).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRIP1	NM_003489.4	c.640A>T	p.Arg214Trp	missense_variant	Exon 4 of 4	ENST00000318948.7	NP_003480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRIP1	ENST00000318948.7	c.640A>T	p.Arg214Trp	missense_variant	Exon 4 of 4	2	NM_003489.4	ENSP00000327213.4
NRIP1	ENST00000400199.5	c.640A>T	p.Arg214Trp	missense_variant	Exon 3 of 3	3		ENSP00000383060.1
NRIP1	ENST00000400202.5	c.640A>T	p.Arg214Trp	missense_variant	Exon 3 of 3	5		ENSP00000383063.1
ENSG00000235609	ENST00000432230.6	n.87+46791A>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461866 Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.4	D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.44
MutPred		0.36		Loss of disorder (P = 0.0012);Loss of disorder (P = 0.0012);Loss of disorder (P = 0.0012);
MVP		0.24
MPC		0.085
ClinPred		0.94	D
GERP RS		1.9
Varity_R		0.33
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-16339874;