rs1263359

chr4-2860299-G-Achr4-2860299-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001354761.2(ADD1):c.-20-15597G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,998 control chromosomes in the GnomAD database, including 20,671 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 0.52 (20671 hom., cov: 32)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

ADD1 (HGNC:243): (adducin 1) Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD1	NM_001354761.2	c.-20-15597G>A		intron_variant		ENST00000683351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD1	ENST00000683351.1	c.-20-15597G>A		intron_variant			NM_001354761.2
	ENST00000664060.1	n.368C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78410 AN: 151880 Hom.: 20636 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.516 AC: 78498 AN: 151998 Hom.: 20671 Cov.: 32 AF XY: 0.513 AC XY: 38090 AN XY: 74276

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.483

Alfa AF: 0.481 Hom.: 6873

Bravo AF: 0.515

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	10
Dann	Benign	0.91

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: rs1263359; hg19: chr4-2862026;