1-154600943-C-T

Variant names:

• chr1-154600943-C-T
• rs3738032
• NM_001111.5:c.1601+98G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001111.5(ADAR):​c.1601+98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,515,114 control chromosomes in the GnomAD database, including 36,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3655 hom., cov: 31)
  • Exomes 𝑓: 0.22 (33055 hom.)
• Consequence: ADAR NM_001111.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.122
• Publications: 10 publications found

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]

ADAR Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• dyschromatosis symmetrica hereditaria

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Aicardi-Goutieres syndrome 6

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial infantile bilateral striatal necrosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-154600943-C-T is Benign according to our data. Variant chr1-154600943-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001111.5	MANE Select	c.1601+98G>A		intron	N/A	NP_001102.3
	ADAR	NM_001365045.1		c.1628+98G>A		intron	N/A	NP_001351974.1
	ADAR	NM_015840.4		c.1601+98G>A		intron	N/A	NP_056655.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.1601+98G>A		intron	N/A	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.716+98G>A		intron	N/A	ENSP00000357456.3
	ADAR	ENST00000463920.5	TSL:2	n.1581G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33014 AN: 151772 Hom.: 3646 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.216 AC: 294910 AN: 1363224 Hom.: 33055 Cov.: 22 AF XY: 0.215 AC XY: 146810 AN XY: 683046

African (AFR) AF: 0.221 AC: 6914 AN: 31328

American (AMR) AF: 0.138 AC: 6072 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5745 AN: 25356

East Asian (EAS) AF: 0.124 AC: 4853 AN: 39226

South Asian (SAS) AF: 0.180 AC: 15021 AN: 83488

European-Finnish (FIN) AF: 0.268 AC: 13841 AN: 51720

Middle Eastern (MID) AF: 0.206 AC: 826 AN: 4002

European-Non Finnish (NFE) AF: 0.223 AC: 229212 AN: 1027012

Other (OTH) AF: 0.218 AC: 12426 AN: 56994

GnomAD4 genome AF: 0.218 AC: 33050 AN: 151890 Hom.: 3655 Cov.: 31 AF XY: 0.216 AC XY: 16019 AN XY: 74256

African (AFR) AF: 0.219 AC: 9085 AN: 41392

American (AMR) AF: 0.187 AC: 2852 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3470

East Asian (EAS) AF: 0.119 AC: 612 AN: 5158

South Asian (SAS) AF: 0.175 AC: 839 AN: 4808

European-Finnish (FIN) AF: 0.277 AC: 2923 AN: 10560

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15220 AN: 67930

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.218 Hom.: 14258

Bravo AF: 0.210

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.60
PhyloP100		-0.12
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: rs3738032; hg19: chr1-154573419; COSMIC: COSV52716096; COSMIC: COSV52716096;