NM_004164.3:c.340G>A

Variant names:

• chr3-139454743-C-T
• rs370436733
• NM_004164.3:c.340G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004164.3(RBP2):​c.340G>A​(p.Asp114Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBP2 NM_004164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

Genes affected

RBP2 (HGNC:9920): (retinol binding protein 2) This gene encodes an abundant protein present in the small intestinal epithelium. It is thought to participate in the uptake and/or intracellular metabolism of vitamin A. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. This protein may also modulate the supply of retinoic acid to the nuclei of endometrial cells during the menstrual cycle. [provided by RefSeq, Aug 2015]

COPB2-DT (HGNC:55579): (COPB2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21374431).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004164.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP2	NM_004164.3	MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 3 of 4	NP_004155.2
	COPB2-DT	NR_121609.1		n.354+31629C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP2	ENST00000232217.6	TSL:1 MANE Select	c.340G>A	p.Asp114Asn	missense	Exon 3 of 4	ENSP00000232217.2	P50120
	RBP2	ENST00000950403.1		c.340G>A	p.Asp114Asn	missense	Exon 4 of 5	ENSP00000620462.1
	COPB2-DT	ENST00000515247.5	TSL:4	n.317+31629C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.027
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.1
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.17
Sift	Benign	0.11	T
Sift4G	Benign	0.15	T
Polyphen		0.0070	B
Vest4		0.28
MutPred		0.65		Gain of MoRF binding (P = 0.0371)
MVP		0.34
MPC		0.23
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.66
gMVP		0.66
Mutation Taster		=63/37	polymorphism

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: rs370436733; hg19: chr3-139173585;