1-234373106-T-A

Position:

• chr1-234373106-T-A

Variant summary

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

The NR_125961.1(COA6-AS1):​n.276A>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 0.0161 in 188,114 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (18 hom., cov: 32)
  • Exomes 𝑓: 0.019 (7 hom.)
• Consequence: COA6-AS1 NR_125961.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.779

Genes affected

COA6-AS1 (HGNC:40825): (COA6 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-234373106-T-A is Benign according to our data. Variant chr1-234373106-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 672594.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 = 0.0154 (2344/152310) while in subpopulation NFE AF= 0.0237 (1611/68020). AF 95% confidence interval is 0.0227. There are 18 homozygotes in gnomad4. There are 1061 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6-AS1	NR_125961.1	n.276A>T		non_coding_transcript_exon_variant	2/2
COA6-AS1	NR_125962.1	n.298A>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6-AS1	ENST00000685022.2	n.559A>T		non_coding_transcript_exon_variant	1/1
COA6-AS1	ENST00000451795.3	n.347A>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2345 AN: 152192 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00434

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0189 AC: 677 AN: 35804 Hom.: 7 Cov.: 0 AF XY: 0.0195 AC XY: 357 AN XY: 18348

Gnomad4 AFR exome AF: 0.00288

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.00925

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0154 AC: 2344 AN: 152310 Hom.: 18 Cov.: 32 AF XY: 0.0142 AC XY: 1061 AN XY: 74472

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00960

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0185 Hom.: 1

Bravo AF: 0.0156

Asia WGS AF: 0.00693 AC: 25 AN: 3478

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	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	-0.72
CADD	Benign	3.8
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141196097; hg19: chr1-234508852;