rs3134613

Positions:

• chr1-39899131-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033081.3(MYCL):​c.497-1161G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 970,376 control chromosomes in the GnomAD database, including 128,703 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 0.58 (27753 hom., cov: 33)
  • Exomes 𝑓: 0.49 (100950 hom.)
• Consequence: MYCL NM_001033081.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

Genes affected

MYCL (HGNC:7555): (MYCL proto-oncogene, bHLH transcription factor) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of inner ear auditory receptor cell differentiation. Located in chromosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYCL-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCL	NM_001033081.3	c.497-1161G>T		intron_variant		ENST00000372816.3	NP_001028253.1
MYCL	NM_001033082.3	c.587-1161G>T		intron_variant			NP_001028254.2
MYCL-AS1	NR_183424.1	n.*33C>A		downstream_gene_variant
MYCL-AS1	NR_183425.1	n.*33C>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCL	ENST00000372816.3	c.497-1161G>T		intron_variant		2	NM_001033081.3	ENSP00000361903.2
MYCL	ENST00000397332.3	c.587-1161G>T		intron_variant		1		ENSP00000380494.2
MYCL-AS1	ENST00000418255.1	n.*33C>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88510 AN: 152006 Hom.: 27700 Cov.: 33

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.494 AC: 403895 AN: 818252 Hom.: 100950 Cov.: 14 AF XY: 0.493 AC XY: 186680 AN XY: 378362

Gnomad4 AFR exome AF: 0.870

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.583 AC: 88615 AN: 152124 Hom.: 27753 Cov.: 33 AF XY: 0.580 AC XY: 43132 AN XY: 74362

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.533

Alfa AF: 0.496 Hom.: 29789

Bravo AF: 0.593

Asia WGS AF: 0.562 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs3134613; hg19: chr1-40364803;