rs3775067

chr4-2886895-G-Achr4-2886895-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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

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	UniProt
ADD1	NM_001354761.2	c.510+2229G>A		intron_variant		ENST00000683351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD1	ENST00000683351.1	c.510+2229G>A		intron_variant			NM_001354761.2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60505 AN: 151804 Hom.: 12355 Cov.: 31

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

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

Other links and lift over

dbSNP: rs3775067; hg19: chr4-2888622;