rs6655975

Positions:

• chr1-150569652-A-G
• chr1-150569652-A-T

Variant summary

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

The NR_104133.1(ADAMTSL4-AS1):​n.592+4007T>C variant causes a intron, non coding transcript 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: ADAMTSL4-AS1 NR_104133.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

Genes affected

ADAMTSL4-AS1 (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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL4-AS1	NR_104133.1	n.592+4007T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCL1	ENST00000678770.1	c.*8-6435T>C		intron_variant				P1
MCL1	ENST00000617352.1	n.592+4007T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.648

Alfa AF: 0.644 Hom.: 63540

Bravo AF: 0.661

Asia WGS AF: 0.626 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6655975; hg19: chr1-150542128;