10-93592093-T-C

Variant names:

• chr10-93592093-T-C
• rs1204359568
• NM_006744.4:c.588A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006744.4(RBP4):​c.588A>G​(p.Ser196Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBP4 NM_006744.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-93592093-T-C is Benign according to our data. Variant chr10-93592093-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2866709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.087 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.588A>G	p.Ser196Ser	synonymous_variant	Exon 6 of 6	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.588A>G	p.Ser196Ser	synonymous_variant	Exon 6 of 6		NP_001310446.1
RBP4	NM_001323518.2	c.582A>G	p.Ser194Ser	synonymous_variant	Exon 6 of 6		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.588A>G	p.Ser196Ser	synonymous_variant	Exon 6 of 6	1	NM_006744.4	ENSP00000360519.3
RBP4	ENST00000371467.5	c.588A>G	p.Ser196Ser	synonymous_variant	Exon 6 of 6	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.582A>G	p.Ser194Ser	synonymous_variant	Exon 6 of 6	5		ENSP00000360524.2
FFAR4	ENST00000604414.1	c.697-11981T>C		intron_variant	Intron 2 of 2	3		ENSP00000474477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 21, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		-0.087

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: rs1204359568; hg19: chr10-95351850;