chr1-150578819-T-C

Variant names:

• chr1-150578819-T-C
• rs35661734
• NM_021960.5:c.688+24A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021960.5(MCL1):​c.688+24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,595,308 control chromosomes in the GnomAD database, including 1,415 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 0.030 (91 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1324 hom.)
• Consequence: MCL1 NM_021960.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0967 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	NM_021960.5	MANE Select	c.688+24A>G		intron	N/A	NP_068779.1
	MCL1	NM_182763.3		c.688+24A>G		intron	N/A	NP_877495.1
	MCL1	NM_001197320.2		c.229+24A>G		intron	N/A	NP_001184249.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	ENST00000369026.3	TSL:1 MANE Select	c.688+24A>G		intron	N/A	ENSP00000358022.2
	MCL1	ENST00000307940.3	TSL:1	c.688+24A>G		intron	N/A	ENSP00000309973.3
	MCL1	ENST00000620947.4	TSL:1	c.229+24A>G		intron	N/A	ENSP00000477624.1

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4553 AN: 152082 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0401

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0394

Gnomad OTH AF: 0.0364

GnomAD2 exomes AF: 0.0375 AC: 8967 AN: 239054 AF XY: 0.0409

Gnomad AFR exome AF: 0.00556

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.0421

Gnomad NFE exome AF: 0.0398

Gnomad OTH exome AF: 0.0464

GnomAD4 exome AF: 0.0391 AC: 56409 AN: 1443108 Hom.: 1324 Cov.: 31 AF XY: 0.0402 AC XY: 28756 AN XY: 715922

African (AFR) AF: 0.00707 AC: 233 AN: 32936

American (AMR) AF: 0.0223 AC: 953 AN: 42730

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 2368 AN: 24886

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39484

South Asian (SAS) AF: 0.0631 AC: 5358 AN: 84878

European-Finnish (FIN) AF: 0.0427 AC: 2246 AN: 52552

Middle Eastern (MID) AF: 0.104 AC: 587 AN: 5662

European-Non Finnish (NFE) AF: 0.0384 AC: 42220 AN: 1100506

Other (OTH) AF: 0.0410 AC: 2439 AN: 59474

GnomAD4 genome AF: 0.0299 AC: 4550 AN: 152200 Hom.: 91 Cov.: 32 AF XY: 0.0305 AC XY: 2269 AN XY: 74402

African (AFR) AF: 0.00725 AC: 301 AN: 41544

American (AMR) AF: 0.0280 AC: 428 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0480 AC: 231 AN: 4814

European-Finnish (FIN) AF: 0.0401 AC: 426 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0394 AC: 2679 AN: 67984

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0378 Hom.: 49

Bravo AF: 0.0276

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.52
DANN	Benign	0.64
PhyloP100		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35661734; hg19: chr1-150551295; COSMIC: COSV107332985; COSMIC: COSV107332985;