rs7090030

Positions:

• chr10-110100915-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356080.9(ADD3):​c.195+67T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,427,598 control chromosomes in the GnomAD database, including 8,989 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 0.14 (5016 hom., cov: 31)
  • Exomes 𝑓: 0.017 (3973 hom.)
• Consequence: ADD3 ENST00000356080.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

ADD3 (HGNC:245): (adducin 3) Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD3	NM_016824.5	c.195+67T>G		intron_variant		ENST00000356080.9	NP_058432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADD3	ENST00000356080.9	c.195+67T>G		intron_variant		1	NM_016824.5	ENSP00000348381	A1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21646 AN: 151964 Hom.: 4991 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0171 AC: 21860 AN: 1275516 Hom.: 3973 AF XY: 0.0162 AC XY: 10117 AN XY: 624970

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.00493

Gnomad4 SAS exome AF: 0.0233

Gnomad4 FIN exome AF: 0.000210

Gnomad4 NFE exome AF: 0.00293

Gnomad4 OTH exome AF: 0.0380

GnomAD4 genome AF: 0.143 AC: 21718 AN: 152082 Hom.: 5016 Cov.: 31 AF XY: 0.138 AC XY: 10277 AN XY: 74358

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.0593

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.111

Alfa AF: 0.138 Hom.: 528

Bravo AF: 0.163

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs7090030; hg19: chr10-111860673;