rs3772875

Variant names:

• chr3-139469276-A-G
• rs3772875
• NM_004164.3:c.74-6986T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBP2	NM_004164.3	c.74-6986T>C		intron_variant	Intron 1 of 3	ENST00000232217.6	NP_004155.2
COPB2-DT	NR_121609.1	n.354+46162A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP2	ENST00000232217.6	c.74-6986T>C		intron_variant	Intron 1 of 3	1	NM_004164.3	ENSP00000232217.2

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

African (AFR) AF: 0.601 AC: 24917 AN: 41470

American (AMR) AF: 0.166 AC: 2530 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 684 AN: 3470

East Asian (EAS) AF: 0.0625 AC: 323 AN: 5166

South Asian (SAS) AF: 0.170 AC: 823 AN: 4828

European-Finnish (FIN) AF: 0.0464 AC: 492 AN: 10608

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9539 AN: 67976

Other (OTH) AF: 0.228 AC: 481 AN: 2112

Alfa AF: 0.191 Hom.: 5986

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
PhyloP100		2.2
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: rs3772875; hg19: chr3-139188118;