rs10488838

Variant names:

• chr4-2879608-A-G
• rs10488838
• NM_001354761.2:c.196-2290A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-2879608-A-G
• chr4-2879608-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 gene

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.196-2290A>G		intron	N/A	NP_001341690.1	A0A804HL01
	ADD1	NM_001354756.2		c.196-2290A>G		intron	N/A	NP_001341685.1
	ADD1	NM_014189.4		c.196-2290A>G		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.196-2290A>G		intron	N/A	ENSP00000508142.1	A0A804HL01
	ADD1	ENST00000355842.7	TSL:1	c.196-2290A>G		intron	N/A	ENSP00000348100.3	P35611-4
	ADD1	ENST00000398123.6	TSL:1	c.196-2290A>G		intron	N/A	ENSP00000381191.2	P35611-6

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

African (AFR) AF: 0.0457 AC: 1892 AN: 41382

American (AMR) AF: 0.0118 AC: 180 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00458 AC: 22 AN: 4804

European-Finnish (FIN) AF: 0.00212 AC: 22 AN: 10362

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00566 AC: 384 AN: 67898

Other (OTH) AF: 0.0166 AC: 35 AN: 2106

Alfa AF: 0.0134 Hom.: 6

Bravo AF: 0.0194

Asia WGS AF: 0.00375 AC: 13 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	0.60
DANN	Benign	0.67
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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: rs10488838; hg19: chr4-2881335;