rs61461737

Variant names:

• chr10-93600623-A-G
• rs61461737
• NM_006744.4:c.248+44T>C

Variant summary

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

The NM_006744.4(RBP4):​c.248+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,611,628 control chromosomes in the GnomAD database, including 4,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (616 hom., cov: 33)
  • Exomes 𝑓: 0.073 (4332 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.419
• Publications: 4 publications found

Genes affected

RBP4 (HGNC:9922): (retinol binding protein 4) This protein belongs to the lipocalin family and is the specific carrier for retinol (vitamin A alcohol) in the blood. It delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin which prevents its loss by filtration through the kidney glomeruli. A deficiency of vitamin A blocks secretion of the binding protein posttranslationally and results in defective delivery and supply to the epidermal cells. [provided by RefSeq, Jul 2008]

FFAR4 (HGNC:19061): (free fatty acid receptor 4) This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-93600623-A-G is Benign according to our data. Variant chr10-93600623-A-G is described in ClinVar as Benign. ClinVar VariationId is 1271228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006744.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	NM_006744.4	MANE Select	c.248+44T>C		intron	N/A	NP_006735.2
	RBP4	NM_001323517.1		c.248+44T>C		intron	N/A	NP_001310446.1
	RBP4	NM_001323518.2		c.242+44T>C		intron	N/A	NP_001310447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBP4	ENST00000371464.8	TSL:1 MANE Select	c.248+44T>C		intron	N/A	ENSP00000360519.3
	FFAR4	ENST00000604414.1	TSL:3	c.697-3451A>G		intron	N/A	ENSP00000474477.1
	RBP4	ENST00000854018.1		c.252+44T>C		intron	N/A	ENSP00000524077.1

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12341 AN: 152140 Hom.: 615 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0871

GnomAD2 exomes AF: 0.0634 AC: 15445 AN: 243520 AF XY: 0.0638

Gnomad AFR exome AF: 0.0951

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.00116

Gnomad FIN exome AF: 0.0765

Gnomad NFE exome AF: 0.0746

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0730 AC: 106595 AN: 1459370 Hom.: 4332 Cov.: 34 AF XY: 0.0728 AC XY: 52812 AN XY: 725828

African (AFR) AF: 0.106 AC: 3539 AN: 33442

American (AMR) AF: 0.0412 AC: 1829 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2848 AN: 26030

East Asian (EAS) AF: 0.000882 AC: 35 AN: 39672

South Asian (SAS) AF: 0.0468 AC: 4021 AN: 85940

European-Finnish (FIN) AF: 0.0746 AC: 3960 AN: 53054

Middle Eastern (MID) AF: 0.138 AC: 793 AN: 5754

European-Non Finnish (NFE) AF: 0.0764 AC: 84867 AN: 1110724

Other (OTH) AF: 0.0780 AC: 4703 AN: 60314

GnomAD4 genome AF: 0.0812 AC: 12357 AN: 152258 Hom.: 616 Cov.: 33 AF XY: 0.0791 AC XY: 5888 AN XY: 74442

African (AFR) AF: 0.105 AC: 4366 AN: 41556

American (AMR) AF: 0.0595 AC: 910 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5166

South Asian (SAS) AF: 0.0428 AC: 207 AN: 4832

European-Finnish (FIN) AF: 0.0743 AC: 787 AN: 10598

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0787 AC: 5352 AN: 68018

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0891 Hom.: 134

Bravo AF: 0.0802

Asia WGS AF: 0.0360 AC: 127 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
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.47
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs61461737; hg19: chr10-95360380;