16-56191028-G-A

Position:

• chr16-56191028-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NR_027078.2(GNAO1-DT):​n.67C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 151,970 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNAO1-DT NR_027078.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55

Genes affected

GNAO1-DT (HGNC:27543): (GNAO1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-56191028-G-A is Benign according to our data. Variant chr16-56191028-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0164 (2487/151970) while in subpopulation NFE AF= 0.0243 (1650/67910). AF 95% confidence interval is 0.0233. There are 35 homozygotes in gnomad4. There are 1191 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNAO1-DT	NR_027078.2	n.67C>T		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNAO1-DT	ENST00000501259.5	n.67C>T		non_coding_transcript_exon_variant	1/5	1
GNAO1-DT	ENST00000662188.1	n.91C>T		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2487 AN: 151854 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0134

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0164 AC: 2487 AN: 151970 Hom.: 35 Cov.: 32 AF XY: 0.0160 AC XY: 1191 AN XY: 74278

Gnomad4 AFR AF: 0.00402

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.0243

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0191 Hom.: 6

Bravo AF: 0.0132

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.6
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs139633798; hg19: chr16-56224940;