chr6-54190039-A-G

Position:

• chr6-54190039-A-G

Variant summary

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

The NM_001281747.2(MLIP):​c.2589+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 676,212 control chromosomes in the GnomAD database, including 133,064 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 0.55 (24755 hom., cov: 32)
  • Exomes 𝑓: 0.64 (108309 hom.)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

Genes affected

MLIP (HGNC:21355): (muscular LMNA interacting protein) Predicted to enable lamin binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of cardiac muscle hypertrophy in response to stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Predicted to be located in nuclear lumen. Predicted to be active in PML body; nuclear envelope; and sarcolemma. [provided by Alliance of Genome Resources, Apr 2022]

MLIP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLIP	NM_001281747.2	c.2589+125A>G		intron_variant		ENST00000502396.6	NP_001268676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000502396.6	c.2589+125A>G		intron_variant		2	NM_001281747.2	ENSP00000426290.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83175 AN: 151872 Hom.: 24763 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.638 AC: 334599 AN: 524224 Hom.: 108309 AF XY: 0.641 AC XY: 177286 AN XY: 276450

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.702

Gnomad4 NFE exome AF: 0.648

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.547 AC: 83161 AN: 151988 Hom.: 24755 Cov.: 32 AF XY: 0.555 AC XY: 41207 AN XY: 74286

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.573

Alfa AF: 0.585 Hom.: 3301

Bravo AF: 0.518

Asia WGS AF: 0.661 AC: 2293 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.77

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: rs9296739; hg19: chr6-54054837;