Variant 1-150578448-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021960.5(MCL1):c.732A>G(p.Lys244=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,144 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

MCL1
NM_021960.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0300

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-150578448-T-C is Benign according to our data. Variant chr1-150578448-T-C is described in ClinVar as [Benign]. Clinvar id is 770854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0107 (15571/1461866) while in subpopulation MID AF= 0.0258 (149/5768). AF 95% confidence interval is 0.0225. There are 102 homozygotes in gnomad4_exome. There are 7822 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MCL1	NM_021960.5 linkuse as main transcript	c.732A>G	p.Lys244=	synonymous_variant	2/3	ENST00000369026.3	NP_068779.1
MCL1	NM_001197320.2 linkuse as main transcript	c.273A>G	p.Lys91=	synonymous_variant	3/4		NP_001184249.1
MCL1	NM_182763.3 linkuse as main transcript	c.688+395A>G		intron_variant			NP_877495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026.3 linkuse as main transcript	c.732A>G	p.Lys244=	synonymous_variant	2/3	1	NM_021960.5	ENSP00000358022	P1	Q07820-1

Frequencies

GnomAD3 genomes

AF:

0.00810

AC:

1233

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00900

AC:

2264

AN:

251462

Hom.:

AF XY:

0.00943

AC XY:

1281

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0107

AC:

15571

AN:

1461866

Hom.:

102

Cov.:

AF XY:

0.0108

AC XY:

7822

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00816

Gnomad4 ASJ exome

AF:

0.0427

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00772

Gnomad4 FIN exome

AF:

0.00268

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00810

AC:

1234

AN:

152278

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

587

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0109

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.00867

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.1

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over