chr15-80404533-G-C

Variant names:

• chr15-80404533-G-C
• NM_014862.4:c.18G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_014862.4(ARNT2):​c.18G>C​(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARNT2 NM_014862.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.716
• Publications: 0 publications found

Genes affected

ARNT2 (HGNC:16876): (aryl hydrocarbon receptor nuclear translocator 2) This gene encodes a member of the basic-helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily of transcription factors. The encoded protein acts as a partner for several sensor proteins of the bHLH-PAS family, forming heterodimers with the sensor proteins that bind regulatory DNA sequences in genes responsive to developmental and environmental stimuli. Under hypoxic conditions, the encoded protein complexes with hypoxia-inducible factor 1alpha in the nucleus and this complex binds to hypoxia-responsive elements in enhancers and promoters of oxygen-responsive genes. A highly similar protein in mouse forms functional complexes with both aryl hydrocarbon receptors and Single-minded proteins, suggesting additional roles for the encoded protein in the metabolism of xenobiotic compounds and the regulation of neurogenesis, respectively. [provided by RefSeq, Dec 2013]

ARNT2-DT (HGNC:56077): (ARNT2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 15-80404533-G-C is Benign according to our data. Variant chr15-80404533-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2017879.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.716 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014862.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	NM_014862.4	MANE Select	c.18G>C	p.Ala6Ala	synonymous	Exon 1 of 19	NP_055677.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT2	ENST00000303329.9	TSL:1 MANE Select	c.18G>C	p.Ala6Ala	synonymous	Exon 1 of 19	ENSP00000307479.4	Q9HBZ2-1
	ARNT2	ENST00000529181.1	TSL:1	n.184G>C		non_coding_transcript_exon	Exon 1 of 5
	ARNT2	ENST00000869656.1		c.18G>C	p.Ala6Ala	synonymous	Exon 1 of 20	ENSP00000539715.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1067052 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 523476

African (AFR) AF: 0.00 AC: 0 AN: 20486

American (AMR) AF: 0.00 AC: 0 AN: 17424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13914

East Asian (EAS) AF: 0.00 AC: 0 AN: 10150

South Asian (SAS) AF: 0.00 AC: 0 AN: 55478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 892114

Other (OTH) AF: 0.00 AC: 0 AN: 38234

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-0.72
PromoterAI		0.016	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr15-80696875;