chr8-37965251-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000025.3(ADRB3):​c.1205+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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.1205+14G>A		intron	N/A	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.1205+14G>A		intron	N/A	ENSP00000343782.3	P13945
	ENSG00000285880	ENST00000647937.1		c.689+14G>A		intron	N/A	ENSP00000497740.1	A0A3B3IT50
	ADRB3	ENST00000520341.2	TSL:6	n.1347G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1349666 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 664412

African (AFR) AF: 0.00 AC: 0 AN: 27726

American (AMR) AF: 0.00 AC: 0 AN: 24698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19660

East Asian (EAS) AF: 0.00 AC: 0 AN: 36096

South Asian (SAS) AF: 0.00 AC: 0 AN: 66460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070362

Other (OTH) AF: 0.00 AC: 0 AN: 55820

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 60

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.5
DANN	Benign	0.86
PhyloP100		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;