rs12503220

chr4-2848415-G-Achr4-2848415-G-T

Variant summary

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

The NM_001354761.2(ADD1):c.-21+4391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,010 control chromosomes in the GnomAD database, including 3,004 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 0.18 (3004 hom., cov: 32)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD1	NM_001354761.2	c.-21+4391G>A		intron_variant		ENST00000683351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD1	ENST00000683351.1	c.-21+4391G>A		intron_variant			NM_001354761.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27575 AN: 151892 Hom.: 3003 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.181 AC: 27572 AN: 152010 Hom.: 3004 Cov.: 32 AF XY: 0.189 AC XY: 14014 AN XY: 74294

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.191

Alfa AF: 0.190 Hom.: 4318

Bravo AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.48

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: rs12503220; hg19: chr4-2850142;