17-4717202-C-T

Variant names:

• chr17-4717202-C-T
• rs7208257
• NM_004313.4:c.358-15C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004313.4(ARRB2):​c.358-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,613,470 control chromosomes in the GnomAD database, including 702,728 homozygotes. 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: 𝑓 0.91 (63213 hom., cov: 31)
  • Exomes 𝑓: 0.94 (639515 hom.)
• Consequence: ARRB2 NM_004313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613
• Publications: 13 publications found

Genes affected

ARRB2 (HGNC:712): (arrestin beta 2) Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. Arrestin beta 2, like arrestin beta 1, was shown to inhibit beta-adrenergic receptor function in vitro. It is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors. Besides the brain, a cDNA for arrestin beta 2 was isolated from thyroid gland, and thus it may also be involved in hormone-specific desensitization of TSH receptors. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

ENSG00000302420 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004313.4. 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
	ARRB2	NM_004313.4	MANE Select	c.358-15C>T		intron	N/A	NP_004304.1
	ARRB2	NM_001257328.2		c.421-15C>T		intron	N/A	NP_001244257.1
	ARRB2	NM_001257330.2		c.358-15C>T		intron	N/A	NP_001244259.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB2	ENST00000269260.7	TSL:1 MANE Select	c.358-15C>T		intron	N/A	ENSP00000269260.2
	ARRB2	ENST00000574954.5	TSL:1	c.-219-15C>T		intron	N/A	ENSP00000466344.1
	ARRB2	ENST00000412477.7	TSL:2	c.421-15C>T		intron	N/A	ENSP00000403701.3

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138397 AN: 152070 Hom.: 63174 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.938 AC: 235678 AN: 251322 AF XY: 0.939

Gnomad AFR exome AF: 0.831

Gnomad AMR exome AF: 0.956

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.922

GnomAD4 exome AF: 0.935 AC: 1366642 AN: 1461282 Hom.: 639515 Cov.: 42 AF XY: 0.936 AC XY: 680464 AN XY: 726972

African (AFR) AF: 0.836 AC: 27979 AN: 33464

American (AMR) AF: 0.952 AC: 42580 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 23090 AN: 26128

East Asian (EAS) AF: 0.999 AC: 39667 AN: 39690

South Asian (SAS) AF: 0.951 AC: 82054 AN: 86242

European-Finnish (FIN) AF: 0.951 AC: 50781 AN: 53390

Middle Eastern (MID) AF: 0.866 AC: 4993 AN: 5764

European-Non Finnish (NFE) AF: 0.935 AC: 1039786 AN: 1111518

Other (OTH) AF: 0.923 AC: 55712 AN: 60364

GnomAD4 genome AF: 0.910 AC: 138491 AN: 152188 Hom.: 63213 Cov.: 31 AF XY: 0.911 AC XY: 67792 AN XY: 74394

African (AFR) AF: 0.835 AC: 34626 AN: 41478

American (AMR) AF: 0.922 AC: 14099 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3066 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5180

South Asian (SAS) AF: 0.956 AC: 4610 AN: 4822

European-Finnish (FIN) AF: 0.948 AC: 10057 AN: 10610

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63828 AN: 68018

Other (OTH) AF: 0.901 AC: 1906 AN: 2116

Alfa AF: 0.914 Hom.: 13398

Bravo AF: 0.905

Asia WGS AF: 0.959 AC: 3337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.59
PhyloP100		0.61
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: rs7208257; hg19: chr17-4620497;