rs9357777

Variant names:

• chr6-53935146-G-A
• rs9357777
• ENST00000431554.2:n.232+4869G>A

Variant summary

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

The ENST00000431554.2(MLIP):​n.232+4869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,914 control chromosomes in the GnomAD database, including 17,248 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 0.47 (17248 hom., cov: 31)
• Consequence: MLIP ENST00000431554.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 5 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

LOC101927189 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927189	NR_125842.1	n.296+4869G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000431554.2	n.232+4869G>A		intron_variant	Intron 1 of 3	1
MLIP	ENST00000505762.1	c.57+4869G>A		intron_variant	Intron 1 of 2	3		ENSP00000423191.1
MLIP	ENST00000511369.5	n.256+4869G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71610 AN: 151794 Hom.: 17232 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.472 AC: 71645 AN: 151914 Hom.: 17248 Cov.: 31 AF XY: 0.474 AC XY: 35182 AN XY: 74252

African (AFR) AF: 0.370 AC: 15351 AN: 41434

American (AMR) AF: 0.535 AC: 8165 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2845 AN: 5158

South Asian (SAS) AF: 0.533 AC: 2557 AN: 4798

European-Finnish (FIN) AF: 0.452 AC: 4764 AN: 10544

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34163 AN: 67928

Other (OTH) AF: 0.499 AC: 1052 AN: 2108

Alfa AF: 0.494 Hom.: 49088

Bravo AF: 0.473

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs9357777; hg19: chr6-53799944;