dbSNP rs878471: 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:

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MCL1	NM_021960.5 link	c.*2104C>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000369026.3	NP_068779.1
MCL1	NM_182763.3 link	c.*2093C>T	3_prime_UTR_variant	Exon 2 of 2		NP_877495.1
MCL1	NM_001197320.2 link	c.*2104C>T	3_prime_UTR_variant	Exon 4 of 4		NP_001184249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026.3 link	c.*2104C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_021960.5	ENSP00000358022.2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over