rs11194981

chr10-110101296-T-Cchr10-110101296-T-G

Variant summary

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

The NM_016824.5(ADD3):c.195+448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,824 control chromosomes in the GnomAD database, including 8,943 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 0.28 (8943 hom., cov: 31)
• Consequence: ADD3 NM_016824.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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 = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD3	NM_016824.5	c.195+448T>C		intron_variant		ENST00000356080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD3	ENST00000356080.9	c.195+448T>C		intron_variant		1	NM_016824.5	A1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42790 AN: 151706 Hom.: 8919 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.282 AC: 42868 AN: 151824 Hom.: 8943 Cov.: 31 AF XY: 0.281 AC XY: 20846 AN XY: 74248

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.263

Alfa AF: 0.239 Hom.: 1545

Bravo AF: 0.297

Asia WGS AF: 0.432 AC: 1501 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	1.4
Dann	Benign	0.31

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: rs11194981; hg19: chr10-111861054;