rs35392872

Positions:

• chr1-150575462-G-A

Variant summary

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

The NM_021960.5(MCL1):​c.*1913C>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 0.0455 in 232,928 control chromosomes in the GnomAD database, including 382 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 0.045 (251 hom., cov: 32)
  • Exomes 𝑓: 0.047 (131 hom.)
• Consequence: MCL1 NM_021960.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCL1	NM_021960.5	c.*1913C>T		3_prime_UTR_variant	3/3	ENST00000369026.3	NP_068779.1
MCL1	NM_182763.3	c.*1902C>T		3_prime_UTR_variant	2/2		NP_877495.1
MCL1	NM_001197320.2	c.*1913C>T		3_prime_UTR_variant	4/4		NP_001184249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026	c.*1913C>T		3_prime_UTR_variant	3/3	1	NM_021960.5	ENSP00000358022.2

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6780 AN: 152160 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0473 AC: 3816 AN: 80650 Hom.: 131 Cov.: 0 AF XY: 0.0480 AC XY: 1779 AN XY: 37062

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0186

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0765

Gnomad4 NFE exome AF: 0.0670

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0445 AC: 6780 AN: 152278 Hom.: 251 Cov.: 32 AF XY: 0.0427 AC XY: 3178 AN XY: 74448

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0708

Gnomad4 NFE AF: 0.0725

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0608 Hom.: 40

Bravo AF: 0.0399

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35392872; hg19: chr1-150547938;