20-44634715-C-T

Position:

• chr20-44634715-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000022.4(ADA):​c.95+1512G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,122 control chromosomes in the GnomAD database, including 31,301 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 0.63 (31301 hom., cov: 34)
• Consequence: ADA NM_000022.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADA	NM_000022.4	c.95+1512G>A		intron_variant		ENST00000372874.9	NP_000013.2
ADA	NM_001322051.2	c.95+1512G>A		intron_variant			NP_001308980.1
ADA	NM_001322050.2	c.-195+1512G>A		intron_variant			NP_001308979.1
ADA	NR_136160.2	n.187+1512G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADA	ENST00000372874.9	c.95+1512G>A		intron_variant		1	NM_000022.4	ENSP00000361965.4
ADA	ENST00000695995.1	c.95+1512G>A		intron_variant				ENSP00000512318.1
ADA	ENST00000695991.1	c.95+1512G>A		intron_variant				ENSP00000512314.1
ADA	ENST00000696038.1	n.95+1512G>A		intron_variant				ENSP00000512344.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96112 AN: 152004 Hom.: 31283 Cov.: 34

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.632 AC: 96162 AN: 152122 Hom.: 31301 Cov.: 34 AF XY: 0.632 AC XY: 46970 AN XY: 74352

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.653

Alfa AF: 0.692 Hom.: 47346

Bravo AF: 0.615

Asia WGS AF: 0.636 AC: 2213 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	0.022
DANN	Benign	0.55

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: rs447833; hg19: chr20-43263356;