ENST00000515192.5:c.-116G>C

Variant names:

• chr1-150876600-C-G
• rs35756904
• ENST00000515192.5:c.-116G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000515192.5(ARNT):​c.-116G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,540,072 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0083 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (9 hom.)
• Consequence: ARNT ENST00000515192.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 2 publications found

Genes affected

ARNT (HGNC:700): (aryl hydrocarbon receptor nuclear translocator) This gene encodes a protein containing a basic helix-loop-helix domain and two characteristic PAS domains along with a PAC domain. The encoded protein binds to ligand-bound aryl hydrocarbon receptor and aids in the movement of this complex to the nucleus, where it promotes the expression of genes involved in xenobiotic metabolism. This protein is also a co-factor for transcriptional regulation by hypoxia-inducible factor 1. Chromosomal translocation of this locus with the ETV6 (ets variant 6) gene on chromosome 12 have been described in leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00833 (1267/152118) while in subpopulation AFR AF = 0.0294 (1221/41508). AF 95% confidence interval is 0.028. There are 24 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1267 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515192.5. 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
	ARNT	NM_001668.4	MANE Select	c.-33G>C		upstream_gene	N/A	NP_001659.1	P27540-1
	ARNT	NM_001350225.2		c.-70G>C		upstream_gene	N/A	NP_001337154.1
	ARNT	NM_001286036.2		c.-33G>C		upstream_gene	N/A	NP_001272965.1	P27540-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARNT	ENST00000515192.5	TSL:1	c.-116G>C		5_prime_UTR	Exon 1 of 23	ENSP00000423851.1	P27540-3
	ARNT	ENST00000471844.6	TSL:2	n.-33G>C		non_coding_transcript_exon	Exon 1 of 17	ENSP00000425899.1	A6NGV6
	ARNT	ENST00000471844.6	TSL:2	n.-33G>C		5_prime_UTR	Exon 1 of 17	ENSP00000425899.1	A6NGV6

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1263 AN: 152014 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00432

GnomAD2 exomes AF: 0.00148 AC: 208 AN: 140304 AF XY: 0.000992

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.000786

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000777

Gnomad OTH exome AF: 0.000246

GnomAD4 exome AF: 0.000807 AC: 1120 AN: 1387954 Hom.: 9 Cov.: 29 AF XY: 0.000668 AC XY: 457 AN XY: 684430

African (AFR) AF: 0.0305 AC: 954 AN: 31304

American (AMR) AF: 0.00113 AC: 40 AN: 35370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24682

East Asian (EAS) AF: 0.00 AC: 0 AN: 35592

South Asian (SAS) AF: 0.000140 AC: 11 AN: 78568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47030

Middle Eastern (MID) AF: 0.000743 AC: 3 AN: 4040

European-Non Finnish (NFE) AF: 0.0000186 AC: 20 AN: 1073862

Other (OTH) AF: 0.00160 AC: 92 AN: 57506

GnomAD4 genome AF: 0.00833 AC: 1267 AN: 152118 Hom.: 24 Cov.: 32 AF XY: 0.00766 AC XY: 570 AN XY: 74364

African (AFR) AF: 0.0294 AC: 1221 AN: 41508

American (AMR) AF: 0.00209 AC: 32 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67930

Other (OTH) AF: 0.00427 AC: 9 AN: 2106

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.00934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.55
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

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

dbSNP: rs35756904; hg19: chr1-150849076;