3-139469276-A-G

Position:

• chr3-139469276-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004164.3(RBP2):​c.74-6986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,108 control chromosomes in the GnomAD database, including 8,660 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 0.26 (8660 hom., cov: 32)
• Consequence: RBP2 NM_004164.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBP2	NM_004164.3	c.74-6986T>C		intron_variant		ENST00000232217.6	NP_004155.2
COPB2-DT	NR_121609.1	n.354+46162A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBP2	ENST00000232217.6	c.74-6986T>C		intron_variant		1	NM_004164.3	ENSP00000232217	P1
COPB2-DT	ENST00000658348.1	n.671+46162A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39875 AN: 151990 Hom.: 8625 Cov.: 32

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.263 AC: 39960 AN: 152108 Hom.: 8660 Cov.: 32 AF XY: 0.256 AC XY: 19014 AN XY: 74372

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.228

Alfa AF: 0.159 Hom.: 2332

Bravo AF: 0.287

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.78

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: rs3772875; hg19: chr3-139188118;