Genetic Variant MCL1:c.*2104C>T (chr1-150575271-G-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_021960.5(MCL1):c.*2104C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 232,890 control chromosomes in the GnomAD database, including 29,025 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 0.47 ( 18287 hom., cov: 31)

Exomes 𝑓: 0.51 ( 10738 hom. )

Consequence

MCL1
NM_021960.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.113

Publications

25 publications found

Variant links:

Genes affected

MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

MCL1 links:

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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 (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021960.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MCL1	NM_021960.5	MANE Select	c.*2104C>T	3_prime_UTR	Exon 3 of 3	NP_068779.1
MCL1	NM_182763.3		c.*2093C>T	3_prime_UTR	Exon 2 of 2	NP_877495.1
MCL1	NM_001197320.2		c.*2104C>T	3_prime_UTR	Exon 4 of 4	NP_001184249.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MCL1	ENST00000369026.3	TSL:1 MANE Select	c.*2104C>T	3_prime_UTR	Exon 3 of 3	ENSP00000358022.2
MCL1	ENST00000620947.4	TSL:1	c.*2104C>T	3_prime_UTR	Exon 4 of 4	ENSP00000477624.1
MCL1	ENST00000464132.2	TSL:2	n.3455C>T	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72135

AN:

151846

Hom.:

18290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.430

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.493

GnomAD4 exome

AF:

0.506

AC:

40984

AN:

80926

Hom.:

10738

Cov.:

AF XY:

0.508

AC XY:

18896

AN XY:

37230

show subpopulations

African (AFR)

AF:

0.304

AC:

1180

AN:

3884

American (AMR)

AF:

0.398

AC:

989

AN:

2488

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

2329

AN:

5108

East Asian (EAS)

AF:

0.385

AC:

4357

AN:

11328

South Asian (SAS)

AF:

0.377

AC:

264

AN:

700

European-Finnish (FIN)

AF:

0.621

AC:

256

AN:

412

Middle Eastern (MID)

AF:

0.433

AC:

213

AN:

492

European-Non Finnish (NFE)

AF:

0.562

AC:

27996

AN:

49772

Other (OTH)

AF:

0.504

AC:

3400

AN:

6742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

965

1929

2894

3858

4823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.475

AC:

72140

AN:

151964

Hom.:

18287

Cov.:

AF XY:

0.476

AC XY:

35311

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.308

AC:

12769

AN:

41436

American (AMR)

AF:

0.432

AC:

6598

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1522

AN:

3470

East Asian (EAS)

AF:

0.430

AC:

2225

AN:

5178

South Asian (SAS)

AF:

0.359

AC:

1729

AN:

4822

European-Finnish (FIN)

AF:

0.644

AC:

6786

AN:

10540

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.572

AC:

38869

AN:

67936

Other (OTH)

AF:

0.488

AC:

1026

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3712

5569

7425

9281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.512

Hom.:

11606

Bravo

AF:

0.450

Asia WGS

AF:

0.421

AC:

1466

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

0.81

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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