rs685893

Variant names:

• chr6-54096986-A-G
• rs685893
• ENST00000514921.5:c.64-24461A>G

Variant summary

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

The ENST00000514921.5(MLIP):​c.64-24461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,958 control chromosomes in the GnomAD database, including 11,115 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 0.38 (11115 hom., cov: 31)
• Consequence: MLIP ENST00000514921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281746.2	c.64-24461A>G		intron_variant	Intron 1 of 11		NP_001268675.1
MLIP	NM_138569.3	c.64-24461A>G		intron_variant	Intron 1 of 12		NP_612636.2
MLIP	XM_005249476.6	c.64-24461A>G		intron_variant	Intron 1 of 13		XP_005249533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000514921.5	c.64-24461A>G		intron_variant	Intron 1 of 11	1		ENSP00000425142.1
MLIP	ENST00000370876.6	c.33+13370A>G		intron_variant	Intron 1 of 6	1		ENSP00000359913.2
MLIP	ENST00000274897.9	c.64-24461A>G		intron_variant	Intron 1 of 12	2		ENSP00000274897.5

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57192 AN: 151838 Hom.: 11087 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.377 AC: 57278 AN: 151958 Hom.: 11115 Cov.: 31 AF XY: 0.372 AC XY: 27597 AN XY: 74266

African (AFR) AF: 0.455 AC: 18864 AN: 41458

American (AMR) AF: 0.452 AC: 6903 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1153 AN: 3466

East Asian (EAS) AF: 0.297 AC: 1527 AN: 5142

South Asian (SAS) AF: 0.287 AC: 1383 AN: 4824

European-Finnish (FIN) AF: 0.281 AC: 2972 AN: 10558

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23340 AN: 67944

Other (OTH) AF: 0.366 AC: 770 AN: 2106

Alfa AF: 0.369 Hom.: 4834

Bravo AF: 0.396

Asia WGS AF: 0.301 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.47
PhyloP100		0.50
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: rs685893; hg19: chr6-53961784;