1-150577390-T-C

Variant names:

• chr1-150577390-T-C
• rs781152860
• ENST00000307940.3:c.790A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_182763.3(MCL1):​c.790A>G​(p.Ile264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MCL1 NM_182763.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.414
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08467704).
• BP6: Variant 1-150577390-T-C is Benign according to our data. Variant chr1-150577390-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3124285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	NM_021960.5	MANE Select	c.1038A>G	p.Ala346Ala	synonymous	Exon 3 of 3	NP_068779.1	Q07820-1
	MCL1	NM_182763.3		c.790A>G	p.Ile264Val	missense	Exon 2 of 2	NP_877495.1	Q07820-2
	MCL1	NM_001197320.2		c.579A>G	p.Ala193Ala	synonymous	Exon 4 of 4	NP_001184249.1	A0A087WT64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	ENST00000307940.3	TSL:1	c.790A>G	p.Ile264Val	missense	Exon 2 of 2	ENSP00000309973.3	Q07820-2
	MCL1	ENST00000369026.3	TSL:1 MANE Select	c.1038A>G	p.Ala346Ala	synonymous	Exon 3 of 3	ENSP00000358022.2	Q07820-1
	MCL1	ENST00000620947.4	TSL:1	c.579A>G	p.Ala193Ala	synonymous	Exon 4 of 4	ENSP00000477624.1	A0A087WT64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251090 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461550 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111900

Other (OTH) AF: 0.0000166 AC: 1 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.94
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.90	T
PhyloP100		-0.41
PROVEAN	Benign	0.60	N
REVEL	Benign	0.074
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.24
MutPred		0.20		Gain of sheet (P = 0.0344)
MVP		0.33
ClinPred		0.068	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs781152860; hg19: chr1-150549866; COSMIC: COSV57191689; COSMIC: COSV57191689;