6-53944181-C-G

Variant names:

• chr6-53944181-C-G
• rs7766181
• ENST00000431554.2:n.232+13904C>G

Variant summary

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

The ENST00000505762.1(MLIP):​c.57+13904C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,922 control chromosomes in the GnomAD database, including 21,302 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 0.52 (21302 hom., cov: 32)
• Consequence: MLIP ENST00000505762.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 2 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 1

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

LOC101927189 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505762.1. 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
	LOC101927189	NR_125842.1		n.296+13904C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000431554.2	TSL:1	n.232+13904C>G		intron	N/A
	MLIP	ENST00000505762.1	TSL:3	c.57+13904C>G		intron	N/A	ENSP00000423191.1	D6R9R6
	MLIP	ENST00000511369.5	TSL:4	n.256+13904C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79032 AN: 151804 Hom.: 21275 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.521 AC: 79106 AN: 151922 Hom.: 21302 Cov.: 32 AF XY: 0.528 AC XY: 39222 AN XY: 74262

African (AFR) AF: 0.517 AC: 21414 AN: 41400

American (AMR) AF: 0.614 AC: 9379 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1419 AN: 3470

East Asian (EAS) AF: 0.907 AC: 4686 AN: 5168

South Asian (SAS) AF: 0.564 AC: 2720 AN: 4820

European-Finnish (FIN) AF: 0.560 AC: 5902 AN: 10540

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31849 AN: 67938

Other (OTH) AF: 0.501 AC: 1058 AN: 2112

Alfa AF: 0.315 Hom.: 709

Bravo AF: 0.530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs7766181; hg19: chr6-53808979;