rs427483

Variant names:

• chr20-44651193-C-G
• rs427483
• NM_000022.4:c.33+382G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-44651193-C-G
• chr20-44651193-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000022.4(ADA):​c.33+382G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,156 control chromosomes in the GnomAD database, including 5,396 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 0.26 (5396 hom., cov: 33)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 7 publications found

Genes affected

ADA (HGNC:186): (adenosine deaminase) This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019]

ADA Gene-Disease associations (from GenCC):

• severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
• Omenn syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA	NM_000022.4	c.33+382G>C		intron_variant	Intron 1 of 11	ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.33+382G>C		intron_variant	Intron 1 of 10		NP_001308980.1
ADA	NM_001322050.2	c.-257+382G>C		intron_variant	Intron 1 of 10		NP_001308979.1
ADA	NR_136160.2	n.125+382G>C		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.33+382G>C		intron_variant	Intron 1 of 11	1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.33+382G>C		intron_variant	Intron 1 of 8			ENSP00000512318.1
ADA	ENST00000695991.1	c.33+382G>C		intron_variant	Intron 1 of 7			ENSP00000512314.1
ADA	ENST00000696038.1	n.33+382G>C		intron_variant	Intron 1 of 8			ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39176 AN: 152038 Hom.: 5394 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.258 AC: 39194 AN: 152156 Hom.: 5396 Cov.: 33 AF XY: 0.255 AC XY: 18946 AN XY: 74386

African (AFR) AF: 0.179 AC: 7442 AN: 41536

American (AMR) AF: 0.340 AC: 5198 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1335 AN: 5152

South Asian (SAS) AF: 0.203 AC: 981 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2623 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20238 AN: 67982

Other (OTH) AF: 0.260 AC: 549 AN: 2114

Alfa AF: 0.0955 Hom.: 144

Bravo AF: 0.263

Asia WGS AF: 0.240 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.43
PhyloP100		-0.31
PromoterAI		-0.017	Neutral
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: rs427483; hg19: chr20-43279834;