rs3775067

Variant names:

• chr4-2886895-G-A
• rs3775067
• NM_001354761.2:c.510+2229G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-2886895-G-A
• chr4-2886895-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	NM_001354761.2	MANE Select	c.510+2229G>A		intron	N/A	NP_001341690.1	A0A804HL01
	ADD1	NM_001354756.2		c.510+2229G>A		intron	N/A	NP_001341685.1
	ADD1	NM_014189.4		c.510+2229G>A		intron	N/A	NP_054908.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	ENST00000683351.1	MANE Select	c.510+2229G>A		intron	N/A	ENSP00000508142.1	A0A804HL01
	ADD1	ENST00000355842.7	TSL:1	c.510+2229G>A		intron	N/A	ENSP00000348100.3	P35611-4
	ADD1	ENST00000398123.6	TSL:1	c.510+2229G>A		intron	N/A	ENSP00000381191.2	P35611-6

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

African (AFR) AF: 0.376 AC: 15571 AN: 41402

American (AMR) AF: 0.471 AC: 7180 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5152

South Asian (SAS) AF: 0.607 AC: 2930 AN: 4830

European-Finnish (FIN) AF: 0.297 AC: 3135 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26618 AN: 67944

Other (OTH) AF: 0.428 AC: 905 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.092
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3775067; hg19: chr4-2888622;