1-154582078-G-GT

Position:

• chr1-154582078-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001111.5(ADAR):​c.*2727_*2728insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 149,016 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (0 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.124

Genes affected

ADAR (HGNC:225): (adenosine deaminase RNA specific) This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0029 (431/148590) while in subpopulation AFR AF= 0.00765 (310/40510). AF 95% confidence interval is 0.00695. There are 2 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAR	NM_001111.5	c.*2727_*2728insA		3_prime_UTR_variant	15/15	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9	c.*2727_*2728insA		3_prime_UTR_variant	15/15	1	NM_001111.5	ENSP00000357459	P3

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 430 AN: 148498 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000877

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00201

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.00391

GnomAD4 exome AF: 0.00469 AC: 2 AN: 426 Hom.: 0 Cov.: 0 AF XY: 0.00391 AC XY: 1 AN XY: 256

Gnomad4 FIN exome AF: 0.00478

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00290 AC: 431 AN: 148590 Hom.: 2 Cov.: 31 AF XY: 0.00284 AC XY: 206 AN XY: 72450

Gnomad4 AFR AF: 0.00765

Gnomad4 AMR AF: 0.000876

Gnomad4 ASJ AF: 0.000585

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00201

Gnomad4 NFE AF: 0.00114

Gnomad4 OTH AF: 0.00387

Bravo AF: 0.00278

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Symmetrical dyschromatosis of extremities Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs754401167; hg19: chr1-154554554;