rs665640

Positions:

• chr6-54122584-T-A

Variant summary

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

The NM_001281747.2(MLIP):​c.252+982T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,050 control chromosomes in the GnomAD database, including 11,602 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 0.39 (11602 hom., cov: 32)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLIP	NM_001281747.2	c.252+982T>A		intron_variant		ENST00000502396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLIP	ENST00000502396.6	c.252+982T>A		intron_variant		2	NM_001281747.2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58596 AN: 151932 Hom.: 11577 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.386 AC: 58674 AN: 152050 Hom.: 11602 Cov.: 32 AF XY: 0.380 AC XY: 28273 AN XY: 74334

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.381

Alfa AF: 0.376 Hom.: 1351

Bravo AF: 0.405

Asia WGS AF: 0.301 AC: 1047 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.3
DANN	Benign	0.90

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: rs665640; hg19: chr6-53987382;