rs11194997

chr10-110130021-G-Achr10-110130021-G-T

Variant summary

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

The NM_016824.5(ADD3):c.1609-342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,016 control chromosomes in the GnomAD database, including 14,286 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 0.35 (14286 hom., cov: 32)
• Consequence: ADD3 NM_016824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD3	NM_016824.5	c.1609-342G>A		intron_variant		ENST00000356080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD3	ENST00000356080.9	c.1609-342G>A		intron_variant		1	NM_016824.5	A1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52980 AN: 151896 Hom.: 14239 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.349 AC: 53093 AN: 152016 Hom.: 14286 Cov.: 32 AF XY: 0.349 AC XY: 25912 AN XY: 74316

Gnomad4 AFR AF: 0.744

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.313

Alfa AF: 0.307 Hom.: 1736

Bravo AF: 0.364

Asia WGS AF: 0.479 AC: 1663 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.4
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11194997; hg19: chr10-111889779;