11-75335183-T-C

Variant names:

• chr11-75335183-T-C
• rs72561778
• NM_004041.5:c.20+16405A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004041.5(ARRB1):​c.20+16405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 242,316 control chromosomes in the GnomAD database, including 2 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 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ARRB1 NM_004041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 2 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]

MIR326 (HGNC:31769): (microRNA 326) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS2: High AC in GnomAd4 at 461 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004041.5. 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
	ARRB1	NM_004041.5	MANE Select	c.20+16405A>G		intron	N/A	NP_004032.2
	ARRB1	NM_020251.4		c.20+16405A>G		intron	N/A	NP_064647.1	P49407-2
	MIR326	NR_029891.1		n.4A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRB1	ENST00000420843.7	TSL:1 MANE Select	c.20+16405A>G		intron	N/A	ENSP00000409581.2	P49407-1
	ARRB1	ENST00000360025.7	TSL:1	c.20+16405A>G		intron	N/A	ENSP00000353124.3	P49407-2
	ARRB1	ENST00000952726.1		c.20+16405A>G		intron	N/A	ENSP00000622785.1

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 460 AN: 152044 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000675 AC: 53 AN: 78508 AF XY: 0.000577

Gnomad AFR exome AF: 0.00868

Gnomad AMR exome AF: 0.000139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000520

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000166 AC: 15 AN: 90154 Hom.: 0 Cov.: 0 AF XY: 0.000208 AC XY: 11 AN XY: 52942

African (AFR) AF: 0.00540 AC: 9 AN: 1668

American (AMR) AF: 0.000131 AC: 1 AN: 7662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2088

East Asian (EAS) AF: 0.00 AC: 0 AN: 2052

South Asian (SAS) AF: 0.00 AC: 0 AN: 15128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21056

Middle Eastern (MID) AF: 0.00110 AC: 2 AN: 1818

European-Non Finnish (NFE) AF: 0.0000562 AC: 2 AN: 35572

Other (OTH) AF: 0.000322 AC: 1 AN: 3110

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152162 Hom.: 2 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74406

African (AFR) AF: 0.0107 AC: 444 AN: 41516

American (AMR) AF: 0.000785 AC: 12 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67990

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00218 Hom.: 0

Bravo AF: 0.00342

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs72561778; hg19: chr11-75046227;