chr1-150578819-T-C

Position:

• chr1-150578819-T-C

Variant summary

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

The ENST00000369026.3(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 ENST00000369026.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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=-0.79).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCL1	NM_021960.5	c.688+24A>G		intron_variant		ENST00000369026.3	NP_068779.1
MCL1	NM_001197320.2	c.229+24A>G		intron_variant			NP_001184249.1
MCL1	NM_182763.3	c.688+24A>G		intron_variant			NP_877495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026.3	c.688+24A>G		intron_variant		1	NM_021960.5	ENSP00000358022	P1

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

GnomAD3 exomes AF: 0.0375 AC: 8967 AN: 239054 Hom.: 237 AF XY: 0.0409 AC XY: 5299 AN XY: 129550

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 SAS exome AF: 0.0638

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

Gnomad4 AFR exome AF: 0.00707

Gnomad4 AMR exome AF: 0.0223

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0631

Gnomad4 FIN exome AF: 0.0427

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0410

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

Gnomad4 AFR AF: 0.00725

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0480

Gnomad4 FIN AF: 0.0401

Gnomad4 NFE AF: 0.0394

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0429 Hom.: 35

Bravo AF: 0.0276

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.52
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs35661734; hg19: chr1-150551295;