4-2886895-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354761.2(ADD1):​c.510+2229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,922 control chromosomes in the GnomAD database, including 12,360 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 0.40 ( 12360 hom., cov: 31)

Consequence

ADD1
NM_001354761.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADD1NM_001354761.2 linkuse as main transcriptc.510+2229G>A intron_variant ENST00000683351.1 NP_001341690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADD1ENST00000683351.1 linkuse as main transcriptc.510+2229G>A intron_variant NM_001354761.2 ENSP00000508142

Frequencies

GnomAD3 genomes
AF:
0.399
AC:
60505
AN:
151804
Hom.:
12355
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.377
Gnomad AMI
AF:
0.327
Gnomad AMR
AF:
0.471
Gnomad ASJ
AF:
0.460
Gnomad EAS
AF:
0.421
Gnomad SAS
AF:
0.605
Gnomad FIN
AF:
0.297
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.392
Gnomad OTH
AF:
0.429
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.398
AC:
60534
AN:
151922
Hom.:
12360
Cov.:
31
AF XY:
0.401
AC XY:
29809
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.376
Gnomad4 AMR
AF:
0.471
Gnomad4 ASJ
AF:
0.460
Gnomad4 EAS
AF:
0.422
Gnomad4 SAS
AF:
0.607
Gnomad4 FIN
AF:
0.297
Gnomad4 NFE
AF:
0.392
Gnomad4 OTH
AF:
0.428
Alfa
AF:
0.362
Hom.:
2410
Bravo
AF:
0.406
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
-0.89
CADD
Benign
1.9
DANN
Benign
0.67
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3775067; hg19: chr4-2888622; API