rs4998

Variant names:

• chr8-37963968-C-G
• rs4998
• NM_000025.3:c.*250G>C

Variant summary

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

The NM_000025.3(ADRB3):​c.*250G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 463,364 control chromosomes in the GnomAD database, including 2,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (750 hom., cov: 32)
  • Exomes 𝑓: 0.087 (1405 hom.)
• Consequence: ADRB3 NM_000025.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0130
• Publications: 10 publications found

Genes affected

ADRB3 (HGNC:288): (adrenoceptor beta 3) The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor is located mainly in the adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Obesity and bodyweight-related disorders are correlated with certain polymorphisms in three subtypes of beta-adrenoceptor, among them, the ADRB3 gene.[provided by RefSeq, Oct 2019]

ENSG00000285880 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-37963968-C-G is Benign according to our data. Variant chr8-37963968-C-G is described in ClinVar as Benign. ClinVar VariationId is 1264874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000025.3. 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
	ADRB3	NM_000025.3	MANE Select	c.*250G>C		3_prime_UTR	Exon 2 of 2	NP_000016.1	P13945

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB3	ENST00000345060.5	TSL:1 MANE Select	c.*250G>C		3_prime_UTR	Exon 2 of 2	ENSP00000343782.3	P13945
	ENSG00000285880	ENST00000647937.1		c.689+1297G>C		intron	N/A	ENSP00000497740.1	A0A3B3IT50

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13866 AN: 152130 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0867 AC: 26973 AN: 311116 Hom.: 1405 Cov.: 2 AF XY: 0.0874 AC XY: 14310 AN XY: 163820

African (AFR) AF: 0.105 AC: 896 AN: 8510

American (AMR) AF: 0.161 AC: 1849 AN: 11500

Ashkenazi Jewish (ASJ) AF: 0.0347 AC: 333 AN: 9602

East Asian (EAS) AF: 0.168 AC: 3390 AN: 20166

South Asian (SAS) AF: 0.115 AC: 3731 AN: 32416

European-Finnish (FIN) AF: 0.0808 AC: 1653 AN: 20458

Middle Eastern (MID) AF: 0.0591 AC: 80 AN: 1354

European-Non Finnish (NFE) AF: 0.0718 AC: 13565 AN: 189024

Other (OTH) AF: 0.0816 AC: 1476 AN: 18086

GnomAD4 genome AF: 0.0914 AC: 13910 AN: 152248 Hom.: 750 Cov.: 32 AF XY: 0.0935 AC XY: 6962 AN XY: 74442

African (AFR) AF: 0.104 AC: 4332 AN: 41548

American (AMR) AF: 0.134 AC: 2041 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

East Asian (EAS) AF: 0.145 AC: 750 AN: 5174

South Asian (SAS) AF: 0.127 AC: 611 AN: 4828

European-Finnish (FIN) AF: 0.0807 AC: 857 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4987 AN: 68008

Other (OTH) AF: 0.0809 AC: 171 AN: 2114

Alfa AF: 0.0833 Hom.: 95

Bravo AF: 0.0974

Asia WGS AF: 0.142 AC: 498 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		-0.013
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: rs4998; hg19: chr8-37821486;