1-154582475-A-AGGGGCATG

Position:

• chr1-154582475-A-AGGGGCATG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001111.5(ADAR):​c.*2330_*2331insCATGCCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (66920 hom., cov: 0)
  • Exomes 𝑓: 1.0 (9 hom.)
• Consequence: ADAR NM_001111.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.745

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAR	NM_001111.5	c.*2330_*2331insCATGCCCC		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.*2330_*2331insCATGCCCC		3_prime_UTR_variant	15/15	1	NM_001111.5	ENSP00000357459	P3

Frequencies

GnomAD3 genomes AF: 0.935 AC: 141642 AN: 151480 Hom.: 66873 Cov.: 0

Gnomad AFR AF: 0.783

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.953

GnomAD4 exome AF: 1.00 AC: 18 AN: 18 Hom.: 9 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.935 AC: 141747 AN: 151600 Hom.: 66920 Cov.: 0 AF XY: 0.937 AC XY: 69425 AN XY: 74084

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.953

Alfa AF: 0.964 Hom.: 2230

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113414804; hg19: chr1-154554951;