6-54147554-G-C

Variant names:

• chr6-54147554-G-C
• rs2797425
• NM_001281747.2:c.2218-1502G>C

Variant summary

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

The NM_001281747.2(MLIP):​c.2218-1502G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,912 control chromosomes in the GnomAD database, including 17,449 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 0.45 (17449 hom., cov: 31)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LOC105375097 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281747.2	c.2218-1502G>C		intron_variant	Intron 4 of 13	ENST00000502396.6	NP_001268676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000502396.6	c.2218-1502G>C		intron_variant	Intron 4 of 13	2	NM_001281747.2	ENSP00000426290.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68569 AN: 151794 Hom.: 17396 Cov.: 31

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.452 AC: 68687 AN: 151912 Hom.: 17449 Cov.: 31 AF XY: 0.444 AC XY: 32967 AN XY: 74226

African (AFR) AF: 0.693 AC: 28701 AN: 41432

American (AMR) AF: 0.495 AC: 7543 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1237 AN: 3466

East Asian (EAS) AF: 0.331 AC: 1701 AN: 5140

South Asian (SAS) AF: 0.297 AC: 1433 AN: 4820

European-Finnish (FIN) AF: 0.280 AC: 2957 AN: 10566

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23837 AN: 67938

Other (OTH) AF: 0.429 AC: 906 AN: 2114

Alfa AF: 0.219 Hom.: 386

Bravo AF: 0.482

Asia WGS AF: 0.343 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.24
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2797425; hg19: chr6-54012352;