1-234373210-A-C

Position:

• chr1-234373210-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_125961.1(COA6-AS1):​n.172T>G variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 429,764 control chromosomes in the GnomAD database, including 2,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1064 hom., cov: 32)
  • Exomes 𝑓: 0.081 (1226 hom.)
• Consequence: COA6-AS1 NR_125961.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.86

Genes affected

COA6-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-234373210-A-C is Benign according to our data. Variant chr1-234373210-A-C is described in ClinVar as [Benign]. Clinvar id is 683484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6-AS1	NR_125961.1	n.172T>G		splice_region_variant, non_coding_transcript_exon_variant	2/2
COA6-AS1	NR_125962.1	n.194T>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6-AS1	ENST00000451795.3	n.243T>G		splice_region_variant, non_coding_transcript_exon_variant	2/2	5
COA6-AS1	ENST00000685022.2	n.455T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16246 AN: 151974 Hom.: 1060 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.0811 AC: 22511 AN: 277672 Hom.: 1226 Cov.: 0 AF XY: 0.0800 AC XY: 11460 AN XY: 143296

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.000498

Gnomad4 SAS exome AF: 0.0505

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0897

Gnomad4 OTH exome AF: 0.0908

GnomAD4 genome AF: 0.107 AC: 16263 AN: 152092 Hom.: 1064 Cov.: 32 AF XY: 0.103 AC XY: 7687 AN XY: 74364

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0475

Gnomad4 NFE AF: 0.0927

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0183 Hom.: 11

Bravo AF: 0.114

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11549817; hg19: chr1-234508956;