NM_002899.5:c.438+20T>C

Variant names:

• chr3-139538761-A-G
• rs2071387
• NM_002899.5:c.438+20T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002899.5(RBP1):​c.438+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,698 control chromosomes in the GnomAD database, including 38,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6568 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31945 hom.)
• Consequence: RBP1 NM_002899.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.973
• Publications: 23 publications found

Genes affected

RBP1 (HGNC:9919): (retinol binding protein 1) This gene encodes the carrier protein involved in the transport of retinol (vitamin A alcohol) from the liver storage site to peripheral tissue. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-139538761-A-G is Benign according to our data. Variant chr3-139538761-A-G is described in ClinVar as Benign. ClinVar VariationId is 1586963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002899.5. 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
	RBP1	NM_002899.5	MANE Select	c.438+20T>C		intron	N/A	NP_002890.2
	RBP1	NM_001130992.3		c.438+20T>C		intron	N/A	NP_001124464.1
	RBP1	NM_001130993.3		c.438+20T>C		intron	N/A	NP_001124465.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP1	ENST00000672186.1	MANE Select	c.438+20T>C		intron	N/A	ENSP00000500931.1
	RBP1	ENST00000492918.1	TSL:1	c.438+20T>C		intron	N/A	ENSP00000429166.1
	RBP1	ENST00000619087.5	TSL:1	c.252+20T>C		intron	N/A	ENSP00000482165.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40955 AN: 152004 Hom.: 6537 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.242 AC: 60707 AN: 251334 AF XY: 0.223

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.197 AC: 288459 AN: 1461576 Hom.: 31945 Cov.: 35 AF XY: 0.193 AC XY: 140650 AN XY: 727118

African (AFR) AF: 0.443 AC: 14817 AN: 33468

American (AMR) AF: 0.467 AC: 20880 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3218 AN: 26136

East Asian (EAS) AF: 0.215 AC: 8551 AN: 39698

South Asian (SAS) AF: 0.173 AC: 14950 AN: 86248

European-Finnish (FIN) AF: 0.194 AC: 10341 AN: 53414

Middle Eastern (MID) AF: 0.188 AC: 1084 AN: 5768

European-Non Finnish (NFE) AF: 0.182 AC: 202541 AN: 1111738

Other (OTH) AF: 0.200 AC: 12077 AN: 60384

GnomAD4 genome AF: 0.270 AC: 41053 AN: 152122 Hom.: 6568 Cov.: 33 AF XY: 0.271 AC XY: 20171 AN XY: 74370

African (AFR) AF: 0.437 AC: 18152 AN: 41494

American (AMR) AF: 0.361 AC: 5522 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1123 AN: 5158

South Asian (SAS) AF: 0.176 AC: 848 AN: 4830

European-Finnish (FIN) AF: 0.193 AC: 2049 AN: 10598

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12303 AN: 67974

Other (OTH) AF: 0.221 AC: 468 AN: 2114

Alfa AF: 0.206 Hom.: 6844

Bravo AF: 0.295

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-0.97
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: rs2071387; hg19: chr3-139257603; COSMIC: COSV51676926; COSMIC: COSV51676926;