rs1014948

Positions:

• chr4-2915749-G-A
• chr4-2915749-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.1948+709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,110 control chromosomes in the GnomAD database, including 4,343 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 0.22 (4343 hom., cov: 32)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADD1	NM_001354761.2	c.1948+709G>A		intron_variant		ENST00000683351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADD1	ENST00000683351.1	c.1948+709G>A		intron_variant			NM_001354761.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33656 AN: 151992 Hom.: 4342 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.221 AC: 33654 AN: 152110 Hom.: 4343 Cov.: 32 AF XY: 0.222 AC XY: 16487 AN XY: 74350

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0355

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.226

Alfa AF: 0.154 Hom.: 340

Bravo AF: 0.204

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.76

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: rs1014948; hg19: chr4-2917476;