rs3755885

Variant names:

• chr4-2886214-C-G
• rs3755885
• NM_001354761.2:c.510+1548C>G

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+1548C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 152,286 control chromosomes in the GnomAD database, including 421 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 0.048 (421 hom., cov: 33)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	NM_001354761.2	MANE Select	c.510+1548C>G		intron	N/A	NP_001341690.1
	ADD1	NM_001354756.2		c.510+1548C>G		intron	N/A	NP_001341685.1
	ADD1	NM_014189.4		c.510+1548C>G		intron	N/A	NP_054908.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	ENST00000683351.1	MANE Select	c.510+1548C>G		intron	N/A	ENSP00000508142.1
	ADD1	ENST00000355842.7	TSL:1	c.510+1548C>G		intron	N/A	ENSP00000348100.3
	ADD1	ENST00000398123.6	TSL:1	c.510+1548C>G		intron	N/A	ENSP00000381191.2

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7238 AN: 152168 Hom.: 420 Cov.: 33

Gnomad AFR AF: 0.00953

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0476 AC: 7243 AN: 152286 Hom.: 421 Cov.: 33 AF XY: 0.0501 AC XY: 3733 AN XY: 74462

African (AFR) AF: 0.00950 AC: 395 AN: 41580

American (AMR) AF: 0.0761 AC: 1164 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5168

South Asian (SAS) AF: 0.111 AC: 533 AN: 4822

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3028 AN: 68024

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0440 Hom.: 31

Bravo AF: 0.0500

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3755885; hg19: chr4-2887941;