dbSNP rs3134613: MYCL:c.497-1161G>T (chr1-39899131-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

13 publications found

Variant links:

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 links:

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

MYCL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033081.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYCL	NM_001033081.3	MANE Select	c.497-1161G>T	intron	N/A	NP_001028253.1	P12524-1
MYCL	NM_001033082.3		c.587-1161G>T	intron	N/A	NP_001028254.2	P12524-3
MYCL-AS1	NR_183424.1		n.*33C>A	downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYCL	ENST00000372816.3	TSL:2 MANE Select	c.497-1161G>T	intron	N/A	ENSP00000361903.2	P12524-1
MYCL	ENST00000397332.3	TSL:1	c.587-1161G>T	intron	N/A	ENSP00000380494.2	P12524-3
MYCL-AS1	ENST00000418255.2	TSL:2	n.*33C>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88510

AN:

152006

Hom.:

27700

Cov.:

show subpopulations

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.:

AF XY:

0.493

AC XY:

186680

AN XY:

378362

show subpopulations

African (AFR)

AF:

0.870

AC:

13517

AN:

15542

American (AMR)

AF:

0.467

AC:

452

AN:

968

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

2741

AN:

5056

East Asian (EAS)

AF:

0.496

AC:

1767

AN:

3562

South Asian (SAS)

AF:

0.528

AC:

8525

AN:

16158

European-Finnish (FIN)

AF:

0.544

AC:

148

AN:

272

Middle Eastern (MID)

AF:

0.492

AC:

782

AN:

1588

European-Non Finnish (NFE)

AF:

0.484

AC:

362202

AN:

748312

Other (OTH)

AF:

0.514

AC:

13761

AN:

26794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9637

19274

28911

38548

48185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14724

29448

44172

58896

73620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.583

AC:

88615

AN:

152124

Hom.:

27753

Cov.:

AF XY:

0.580

AC XY:

43132

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.835

AC:

34685

AN:

41522

American (AMR)

AF:

0.488

AC:

7455

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1858

AN:

3464

East Asian (EAS)

AF:

0.500

AC:

2588

AN:

5172

South Asian (SAS)

AF:

0.517

AC:

2494

AN:

4826

European-Finnish (FIN)

AF:

0.504

AC:

5321

AN:

10558

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.481

AC:

32702

AN:

67984

Other (OTH)

AF:

0.533

AC:

1123

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1754

3508

5261

7015

8769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.520

Hom.:

58123

Bravo

AF:

0.593

Asia WGS

AF:

0.562

AC:

1956

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over