chr1-150579854-G-T

Variant names:

• chr1-150579854-G-T
• rs3738484
• ENST00000702780.2:n.26G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000702780.2(ENSG00000290074):​n.26G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 291,584 control chromosomes in the GnomAD database, including 36,629 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 0.43 (15887 hom., cov: 30)
  • Exomes 𝑓: 0.53 (20742 hom.)
• Consequence: ENSG00000290074 ENST00000702780.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 8 publications found

Genes affected

ENSG00000290074 (HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCL1	NM_021960.5	c.-324C>A		upstream_gene_variant		ENST00000369026.3	NP_068779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026.3	c.-324C>A		upstream_gene_variant		1	NM_021960.5	ENSP00000358022.2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65176 AN: 151486 Hom.: 15893 Cov.: 30

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.528 AC: 73867 AN: 139982 Hom.: 20742 AF XY: 0.527 AC XY: 37068 AN XY: 70332

African (AFR) AF: 0.217 AC: 1052 AN: 4850

American (AMR) AF: 0.413 AC: 1615 AN: 3910

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 2408 AN: 5842

East Asian (EAS) AF: 0.411 AC: 5123 AN: 12450

South Asian (SAS) AF: 0.424 AC: 2241 AN: 5290

European-Finnish (FIN) AF: 0.644 AC: 4443 AN: 6904

Middle Eastern (MID) AF: 0.414 AC: 316 AN: 764

European-Non Finnish (NFE) AF: 0.574 AC: 51737 AN: 90186

Other (OTH) AF: 0.504 AC: 4932 AN: 9786

GnomAD4 genome AF: 0.430 AC: 65165 AN: 151602 Hom.: 15887 Cov.: 30 AF XY: 0.431 AC XY: 31916 AN XY: 74026

African (AFR) AF: 0.213 AC: 8819 AN: 41438

American (AMR) AF: 0.406 AC: 6194 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3464

East Asian (EAS) AF: 0.422 AC: 2147 AN: 5082

South Asian (SAS) AF: 0.323 AC: 1554 AN: 4810

European-Finnish (FIN) AF: 0.623 AC: 6529 AN: 10484

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.547 AC: 37038 AN: 67764

Other (OTH) AF: 0.451 AC: 949 AN: 2106

Alfa AF: 0.484 Hom.: 3203

Bravo AF: 0.404

Asia WGS AF: 0.395 AC: 1369 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		2.3
PromoterAI		0.041	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3738484; hg19: chr1-150552330;