rs4997

Variant names:

• chr8-37965251-C-A
• rs4997
• NM_000025.3:c.1205+14G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-37965251-C-A
• chr8-37965251-C-T

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.1205+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,501,686 control chromosomes in the GnomAD database, including 5,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (748 hom., cov: 33)
  • Exomes 𝑓: 0.084 (5109 hom.)
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.323
• Publications: 8 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=-0.76).
• BP6: Variant 8-37965251-C-A is Benign according to our data. Variant chr8-37965251-C-A is described in ClinVar as [Benign]. Clinvar id is 1230608.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3	c.1205+14G>T		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.1205+14G>T		intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3
ENSG00000285880	ENST00000647937.1	c.689+14G>T		intron_variant	Intron 1 of 1			ENSP00000497740.1
ADRB3	ENST00000520341.2	n.1347G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13852 AN: 152178 Hom.: 740 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0641

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0812

GnomAD2 exomes AF: 0.0934 AC: 10921 AN: 116978 AF XY: 0.0897

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.0770

Gnomad NFE exome AF: 0.0663

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0837 AC: 112911 AN: 1349392 Hom.: 5109 Cov.: 31 AF XY: 0.0840 AC XY: 55808 AN XY: 664276

African (AFR) AF: 0.103 AC: 2868 AN: 27716

American (AMR) AF: 0.169 AC: 4170 AN: 24638

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 731 AN: 19658

East Asian (EAS) AF: 0.165 AC: 5948 AN: 36086

South Asian (SAS) AF: 0.122 AC: 8103 AN: 66440

European-Finnish (FIN) AF: 0.0819 AC: 3662 AN: 44710

Middle Eastern (MID) AF: 0.0586 AC: 241 AN: 4116

European-Non Finnish (NFE) AF: 0.0770 AC: 82378 AN: 1070214

Other (OTH) AF: 0.0862 AC: 4810 AN: 55814

GnomAD4 genome AF: 0.0912 AC: 13896 AN: 152294 Hom.: 748 Cov.: 33 AF XY: 0.0933 AC XY: 6949 AN XY: 74466

African (AFR) AF: 0.104 AC: 4328 AN: 41578

American (AMR) AF: 0.133 AC: 2041 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.145 AC: 746 AN: 5160

South Asian (SAS) AF: 0.127 AC: 611 AN: 4826

European-Finnish (FIN) AF: 0.0808 AC: 858 AN: 10618

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0733 AC: 4984 AN: 68030

Other (OTH) AF: 0.0808 AC: 171 AN: 2116

Alfa AF: 0.0433 Hom.: 60

Bravo AF: 0.0974

Asia WGS AF: 0.143 AC: 500 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 18, 2018

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	-0.76
CADD	Benign	7.8
DANN	Benign	0.53
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4997; hg19: chr8-37822769; COSMIC: COSV61461715;