4-2860299-G-A

Variant names:

• chr4-2860299-G-A
• rs1263359
• NM_001354761.2:c.-20-15597G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000287099 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354761.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	NM_001354761.2	MANE Select	c.-20-15597G>A		intron	N/A	NP_001341690.1
	ADD1	NM_001354756.2		c.-20-15597G>A		intron	N/A	NP_001341685.1
	ADD1	NM_014189.4		c.-20-15597G>A		intron	N/A	NP_054908.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	ENST00000683351.1	MANE Select	c.-20-15597G>A		intron	N/A	ENSP00000508142.1
	ADD1	ENST00000355842.7	TSL:1	c.-178-7673G>A		intron	N/A	ENSP00000348100.3
	ENSG00000287099	ENST00000664060.1		n.368C>T		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.603 AC: 24991 AN: 41438

American (AMR) AF: 0.433 AC: 6622 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2654 AN: 5170

South Asian (SAS) AF: 0.326 AC: 1565 AN: 4804

European-Finnish (FIN) AF: 0.556 AC: 5863 AN: 10552

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33544 AN: 67968

Other (OTH) AF: 0.483 AC: 1021 AN: 2114

Alfa AF: 0.490 Hom.: 11191

Bravo AF: 0.515

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs1263359; hg19: chr4-2862026;