rs878471

chr1-150575271-G-Achr1-150575271-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
MCL1	NM_021960.5	c.*2104C>T		3_prime_UTR_variant	3/3	ENST00000369026.3
MCL1	NM_001197320.2	c.*2104C>T		3_prime_UTR_variant	4/4
MCL1	NM_182763.3	c.*2093C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCL1	ENST00000369026.3	c.*2104C>T		3_prime_UTR_variant	3/3	1	NM_021960.5	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72135 AN: 151846 Hom.: 18290 Cov.: 31

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.: 0 AF XY: 0.508 AC XY: 18896 AN XY: 37230

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.621

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.475 AC: 72140 AN: 151964 Hom.: 18287 Cov.: 31 AF XY: 0.476 AC XY: 35311 AN XY: 74260

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.488

Alfa AF: 0.519 Hom.: 5577

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	11
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs878471; hg19: chr1-150547747; COSMIC: COSV57190785; COSMIC: COSV57190785;