rs17133921

Variant names:

• chr11-75323942-G-A
• rs17133921
• NM_004041.5:c.20+27646C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-75323942-G-A
• chr11-75323942-G-C
• chr11-75323942-G-T

Variant summary

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

The NM_004041.5(ARRB1):​c.20+27646C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,076 control chromosomes in the GnomAD database, including 1,044 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 0.10 (1044 hom., cov: 32)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 7 publications found

Genes affected

ARRB1 (HGNC:711): (arrestin beta 1) 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 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/beta-arrestin system is believed to play a major role in regulating receptor-mediated immune functions. Alternatively spliced transcripts encoding different isoforms of arrestin beta 1 have been described. [provided by RefSeq, Jan 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRB1	NM_004041.5	c.20+27646C>T		intron_variant	Intron 1 of 15	ENST00000420843.7	NP_004032.2
ARRB1	NM_020251.4	c.20+27646C>T		intron_variant	Intron 1 of 14		NP_064647.1
ARRB1	XM_017017752.3	c.20+27646C>T		intron_variant	Intron 1 of 16		XP_016873241.1
ARRB1	XM_017017754.3	c.20+27646C>T		intron_variant	Intron 1 of 15		XP_016873243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRB1	ENST00000420843.7	c.20+27646C>T		intron_variant	Intron 1 of 15	1	NM_004041.5	ENSP00000409581.2
ARRB1	ENST00000360025.7	c.20+27646C>T		intron_variant	Intron 1 of 14	1		ENSP00000353124.3
ARRB1	ENST00000533255.1	n.73+27646C>T		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15870 AN: 151958 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.0934

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15899 AN: 152076 Hom.: 1044 Cov.: 32 AF XY: 0.101 AC XY: 7531 AN XY: 74354

African (AFR) AF: 0.182 AC: 7525 AN: 41458

American (AMR) AF: 0.0716 AC: 1094 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5180

South Asian (SAS) AF: 0.0614 AC: 296 AN: 4822

European-Finnish (FIN) AF: 0.0522 AC: 552 AN: 10572

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5625 AN: 67978

Other (OTH) AF: 0.0953 AC: 201 AN: 2110

Alfa AF: 0.0860 Hom.: 1046

Bravo AF: 0.109

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		-0.63
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: rs17133921; hg19: chr11-75034986;