NM_000025.3:c.1206-96A>G

Variant names:

• chr8-37964335-T-C
• rs2071493
• NM_000025.3:c.1206-96A>G

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.1206-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,143,280 control chromosomes in the GnomAD database, including 5,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (747 hom., cov: 32)
  • Exomes 𝑓: 0.084 (4269 hom.)
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.198
• Publications: 2 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=-0.83).
• BP6: Variant 8-37964335-T-C is Benign according to our data. Variant chr8-37964335-T-C is described in ClinVar as [Benign]. Clinvar id is 1244998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3	c.1206-96A>G		intron_variant	Intron 1 of 1	ENST00000345060.5	NP_000016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB3	ENST00000345060.5	c.1206-96A>G		intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3
ENSG00000285880	ENST00000647937.1	c.689+930A>G		intron_variant	Intron 1 of 1			ENSP00000497740.1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13835 AN: 151866 Hom.: 738 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0815

GnomAD4 exome AF: 0.0844 AC: 83709 AN: 991294 Hom.: 4269 AF XY: 0.0847 AC XY: 43019 AN XY: 507970

African (AFR) AF: 0.104 AC: 2424 AN: 23396

American (AMR) AF: 0.191 AC: 6734 AN: 35294

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 808 AN: 22016

East Asian (EAS) AF: 0.166 AC: 5941 AN: 35746

South Asian (SAS) AF: 0.120 AC: 8549 AN: 71378

European-Finnish (FIN) AF: 0.0816 AC: 4059 AN: 49722

Middle Eastern (MID) AF: 0.0651 AC: 301 AN: 4622

European-Non Finnish (NFE) AF: 0.0727 AC: 51192 AN: 704598

Other (OTH) AF: 0.0831 AC: 3701 AN: 44522

GnomAD4 genome AF: 0.0913 AC: 13880 AN: 151986 Hom.: 747 Cov.: 32 AF XY: 0.0934 AC XY: 6940 AN XY: 74304

African (AFR) AF: 0.104 AC: 4327 AN: 41452

American (AMR) AF: 0.134 AC: 2040 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 125 AN: 3464

East Asian (EAS) AF: 0.144 AC: 740 AN: 5142

South Asian (SAS) AF: 0.127 AC: 612 AN: 4812

European-Finnish (FIN) AF: 0.0807 AC: 853 AN: 10574

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

European-Non Finnish (NFE) AF: 0.0732 AC: 4976 AN: 67952

Other (OTH) AF: 0.0811 AC: 171 AN: 2108

Alfa AF: 0.0354 Hom.: 15

Bravo AF: 0.0975

Asia WGS AF: 0.142 AC: 497 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

- -

Jun 18, 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	-0.83
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		-0.20
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: rs2071493; hg19: chr8-37821853; COSMIC: COSV61461636; COSMIC: COSV61461636;