chr1-150569652-A-G

Variant names:

• chr1-150569652-A-G
• rs6655975
• ENST00000678770.1:c.*8-6435T>C

Variant summary

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

The ENST00000678770.1(MCL1):​c.*8-6435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,996 control chromosomes in the GnomAD database, including 33,497 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 0.66 (33497 hom., cov: 31)
• Consequence: MCL1 ENST00000678770.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 24 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]

ADAMTSL4-AS1 (HGNC:32041): (ADAMTSL4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000678770.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4-AS1	NR_104133.1		n.592+4007T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCL1	ENST00000678770.1		c.*8-6435T>C		intron	N/A	ENSP00000502859.1	Q07820-1
	MCL1	ENST00000617352.1	TSL:5	n.592+4007T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100478 AN: 151878 Hom.: 33462 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100566 AN: 151996 Hom.: 33497 Cov.: 31 AF XY: 0.661 AC XY: 49078 AN XY: 74290

African (AFR) AF: 0.713 AC: 29540 AN: 41436

American (AMR) AF: 0.609 AC: 9299 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1997 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3450 AN: 5164

South Asian (SAS) AF: 0.479 AC: 2307 AN: 4820

European-Finnish (FIN) AF: 0.723 AC: 7637 AN: 10568

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44202 AN: 67964

Other (OTH) AF: 0.648 AC: 1366 AN: 2108

Alfa AF: 0.647 Hom.: 101178

Bravo AF: 0.661

Asia WGS AF: 0.626 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.33
PhyloP100		-0.076

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6655975;

hg19: chr1-150542128;