chr16-31464292-TAAAAAAAAAAAAA-T

Variant names:

• chr16-31464292-TAAAAAAAAAAAAA-T
• rs537788230
• NM_001105247.2:c.1371-90_1371-78delAAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001105247.2(ARMC5):​c.1371-90_1371-78delAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 499,418 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: ARMC5 NM_001105247.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000219 (26/118806) while in subpopulation EAS AF= 0.00389 (16/4112). AF 95% confidence interval is 0.00244. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC5	NM_001105247.2	c.1371-90_1371-78delAAAAAAAAAAAAA		intron_variant	Intron 3 of 5	ENST00000268314.9	NP_001098717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC5	ENST00000268314.9	c.1371-101_1371-89delAAAAAAAAAAAAA		intron_variant	Intron 3 of 5	5	NM_001105247.2	ENSP00000268314.4

Frequencies

GnomAD3 genomes AF: 0.000219 AC: 26 AN: 118798 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000171

Gnomad ASJ AF: 0.00266

Gnomad EAS AF: 0.00388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000255 AC: 97 AN: 380612 Hom.: 2 AF XY: 0.000270 AC XY: 52 AN XY: 192342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00329

Gnomad4 EAS exome AF: 0.00304

Gnomad4 SAS exome AF: 0.0000601

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000329

Gnomad4 OTH exome AF: 0.000157

GnomAD4 genome AF: 0.000219 AC: 26 AN: 118806 Hom.: 0 Cov.: 27 AF XY: 0.000211 AC XY: 12 AN XY: 56788

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000171

Gnomad4 ASJ AF: 0.00266

Gnomad4 EAS AF: 0.00389

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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: rs537788230; hg19: chr16-31475613;