4-2927878-G-C

Variant names:

• chr4-2927878-G-C
• rs2071694
• NM_001354761.2:c.2048-293G>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.2048-293G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 152,222 control chromosomes in the GnomAD database, including 194 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 0.010 (194 hom., cov: 32)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 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.2048-293G>C		intron	N/A	NP_001341690.1
	ADD1	NM_001354756.2		c.1955-293G>C		intron	N/A	NP_001341685.1
	ADD1	NM_014189.4		c.1955-293G>C		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.2048-293G>C		intron	N/A	ENSP00000508142.1
	ADD1	ENST00000355842.7	TSL:1	c.1989-293G>C		intron	N/A	ENSP00000348100.3
	ADD1	ENST00000398123.6	TSL:1	c.1989-293G>C		intron	N/A	ENSP00000381191.2

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1566 AN: 152104 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0103 AC: 1568 AN: 152222 Hom.: 194 Cov.: 32 AF XY: 0.0115 AC XY: 857 AN XY: 74408

African (AFR) AF: 0.00132 AC: 55 AN: 41544

American (AMR) AF: 0.00176 AC: 27 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1382 AN: 5138

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00402 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.43
PhyloP100		-0.59
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: rs2071694; hg19: chr4-2929605;