rs10488838

Positions:

• chr4-2879608-A-G
• chr4-2879608-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001354761.2(ADD1):​c.196-2290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 151,654 control chromosomes in the GnomAD database, including 56 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 0.017 (56 hom., cov: 31)
• Consequence: ADD1 NM_001354761.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422

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=-0.92).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0175 (2653/151654) while in subpopulation AFR AF= 0.0457 (1892/41382). AF 95% confidence interval is 0.044. There are 56 homozygotes in gnomad4. There are 1293 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 56 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADD1	NM_001354761.2	c.196-2290A>G		intron_variant		ENST00000683351.1	NP_001341690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADD1	ENST00000683351.1	c.196-2290A>G		intron_variant			NM_001354761.2	ENSP00000508142

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2649 AN: 151546 Hom.: 57 Cov.: 31

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00457

Gnomad FIN AF: 0.00212

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00565

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0175 AC: 2653 AN: 151654 Hom.: 56 Cov.: 31 AF XY: 0.0175 AC XY: 1293 AN XY: 74082

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00458

Gnomad4 FIN AF: 0.00212

Gnomad4 NFE AF: 0.00566

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0116 Hom.: 5

Bravo AF: 0.0194

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.67

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: rs10488838; hg19: chr4-2881335;