Genetic Variant NM_001105247.2:c.1371-85_1371-78delAAAAAAAA (chr16-31464292-TAAAAAAAA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is . The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001105247.2(ARMC5):c.1371-85_1371-78delAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 499,446 control chromosomes in the GnomAD database, including 280 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.040 ( 264 hom., cov: 27)

Exomes 𝑓: 0.0048 ( 16 hom. )

Consequence

ARMC5
NM_001105247.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

0 publications found

Variant links:

Genes affected

ARMC5 (HGNC:25781): (armadillo repeat containing 5) This gene encodes a member of the ARM (armadillo/beta-catenin-like repeat) superfamily. The ARM repeat is a tandemly repeated sequence motif with approximately 40 amino acid long. This repeat is implicated in mediating protein-protein interactions. The encoded protein contains seven ARM repeats. Mutations in this gene are associated with primary bilateral macronodular adrenal hyperplasia, which is also known as ACTH-independent macronodular adrenal hyperplasia 2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ARMC5 Gene-Disease associations (from GenCC):

ACTH-independent macronodular adrenal hyperplasia 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
Cushing syndrome due to macronodular adrenal hyperplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ARMC5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001105247.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105247.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMC5	NM_001105247.2	MANE Select	c.1371-85_1371-78delAAAAAAAA	intron	N/A	NP_001098717.1	Q96C12-1
ARMC5	NM_001288767.2		c.1656-85_1656-78delAAAAAAAA	intron	N/A	NP_001275696.1	J3KQ26
ARMC5	NM_001301820.1		c.1467-85_1467-78delAAAAAAAA	intron	N/A	NP_001288749.1	Q96C12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARMC5	ENST00000268314.9	TSL:5 MANE Select	c.1371-101_1371-94delAAAAAAAA	intron	N/A	ENSP00000268314.4	Q96C12-1
ARMC5	ENST00000457010.6	TSL:1	c.1371-101_1371-94delAAAAAAAA	intron	N/A	ENSP00000399561.2	Q96C12-4
ARMC5	ENST00000408912.7	TSL:2	c.1656-101_1656-94delAAAAAAAA	intron	N/A	ENSP00000386125.3	J3KQ26

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

4721

AN:

118836

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000942

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0124

Gnomad NFE

AF:

0.000460

Gnomad OTH

AF:

0.0247

GnomAD4 exome

AF:

0.00481

AC:

1832

AN:

380596

Hom.:

AF XY:

0.00436

AC XY:

838

AN XY:

192334

show subpopulations

African (AFR)

AF:

0.157

AC:

1411

AN:

8992

American (AMR)

AF:

0.0115

AC:

AN:

8120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8520

East Asian (EAS)

AF:

0.00

AC:

AN:

18406

South Asian (SAS)

AF:

0.000541

AC:

AN:

16646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25902

Middle Eastern (MID)

AF:

0.00888

AC:

AN:

1464

European-Non Finnish (NFE)

AF:

0.000347

AC:

AN:

273400

Other (OTH)

AF:

0.0110

AC:

211

AN:

19146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0398

AC:

4732

AN:

118850

Hom.:

264

Cov.:

AF XY:

0.0389

AC XY:

2211

AN XY:

56812

show subpopulations

African (AFR)

AF:

0.142

AC:

4488

AN:

31706

American (AMR)

AF:

0.0149

AC:

174

AN:

11674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3008

East Asian (EAS)

AF:

0.00

AC:

AN:

4112

South Asian (SAS)

AF:

0.000631

AC:

AN:

3170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6034

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.000460

AC:

AN:

56570

Other (OTH)

AF:

0.0247

AC:

AN:

1582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.574

Heterozygous variant carriers

164

329

493

658

822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over