10-93593731-C-T

Variant names:

• chr10-93593731-C-T
• rs10882275
• NM_006744.4:c.568+92G>A

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.568+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,405,670 control chromosomes in the GnomAD database, including 17,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1553 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15883 hom.)
• Consequence: RBP4 NM_006744.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.269
• Publications: 3 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=-0.78).
• BP6: Variant 10-93593731-C-T is Benign according to our data. Variant chr10-93593731-C-T is described in ClinVar as [Benign]. Clinvar id is 1247112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBP4	NM_006744.4	c.568+92G>A		intron_variant	Intron 5 of 5	ENST00000371464.8	NP_006735.2
RBP4	NM_001323517.1	c.568+92G>A		intron_variant	Intron 5 of 5		NP_001310446.1
RBP4	NM_001323518.2	c.562+92G>A		intron_variant	Intron 5 of 5		NP_001310447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBP4	ENST00000371464.8	c.568+92G>A		intron_variant	Intron 5 of 5	1	NM_006744.4	ENSP00000360519.3
FFAR4	ENST00000604414.1	c.697-10343C>T		intron_variant	Intron 2 of 2	3		ENSP00000474477.1
RBP4	ENST00000371467.5	c.568+92G>A		intron_variant	Intron 5 of 5	5		ENSP00000360522.1
RBP4	ENST00000371469.2	c.562+92G>A		intron_variant	Intron 5 of 5	5		ENSP00000360524.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20022 AN: 151976 Hom.: 1552 Cov.: 32

Gnomad AFR AF: 0.0883

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.151 AC: 189744 AN: 1253576 Hom.: 15883 AF XY: 0.150 AC XY: 94814 AN XY: 633152

African (AFR) AF: 0.0871 AC: 2560 AN: 29404

American (AMR) AF: 0.0726 AC: 3203 AN: 44096

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4062 AN: 24870

East Asian (EAS) AF: 0.00152 AC: 59 AN: 38830

South Asian (SAS) AF: 0.0750 AC: 6121 AN: 81660

European-Finnish (FIN) AF: 0.185 AC: 7613 AN: 41250

Middle Eastern (MID) AF: 0.165 AC: 623 AN: 3776

European-Non Finnish (NFE) AF: 0.168 AC: 157484 AN: 935916

Other (OTH) AF: 0.149 AC: 8019 AN: 53774

GnomAD4 genome AF: 0.132 AC: 20024 AN: 152094 Hom.: 1553 Cov.: 32 AF XY: 0.131 AC XY: 9735 AN XY: 74350

African (AFR) AF: 0.0882 AC: 3660 AN: 41506

American (AMR) AF: 0.0979 AC: 1496 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3464

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5168

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2079 AN: 10560

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11385 AN: 67976

Other (OTH) AF: 0.124 AC: 262 AN: 2110

Alfa AF: 0.148 Hom.: 660

Bravo AF: 0.123

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.38
PhyloP100		-0.27
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: rs10882275; hg19: chr10-95353488;