rs17833172

Variant names:

• chr4-2866787-G-A
• rs17833172
• NM_001354761.2:c.-20-9109G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354761.2(ADD1):​c.-20-9109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,050 control chromosomes in the GnomAD database, including 4,647 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 0.23 (4647 hom., cov: 32)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADD1	NM_001354761.2	c.-20-9109G>A		intron_variant	Intron 1 of 15	ENST00000683351.1	NP_001341690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADD1	ENST00000683351.1	c.-20-9109G>A		intron_variant	Intron 1 of 15		NM_001354761.2	ENSP00000508142.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35100 AN: 151932 Hom.: 4647 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.231 AC: 35106 AN: 152050 Hom.: 4647 Cov.: 32 AF XY: 0.232 AC XY: 17227 AN XY: 74304

African (AFR) AF: 0.143 AC: 5937 AN: 41502

American (AMR) AF: 0.200 AC: 3062 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3466

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5174

South Asian (SAS) AF: 0.120 AC: 578 AN: 4828

European-Finnish (FIN) AF: 0.379 AC: 3995 AN: 10540

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19539 AN: 67952

Other (OTH) AF: 0.238 AC: 502 AN: 2112

Alfa AF: 0.267 Hom.: 7135

Bravo AF: 0.215

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.65
PhyloP100		-1.0
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: rs17833172; hg19: chr4-2868514;