chr6-54105520-T-G

Position:

• chr6-54105520-T-G

Variant summary

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

The ENST00000514921.5(MLIP):​c.64-15927T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,070 control chromosomes in the GnomAD database, including 12,102 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 (12102 hom., cov: 32)
• Consequence: MLIP ENST00000514921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLIP	NM_001281746.2	c.64-15927T>G		intron_variant			NP_001268675.1
MLIP	NM_138569.3	c.64-15927T>G		intron_variant			NP_612636.2
MLIP	XM_005249476.6	c.64-15927T>G		intron_variant			XP_005249533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000370876.6	c.34-18953T>G		intron_variant		1		ENSP00000359913
MLIP	ENST00000514921.5	c.64-15927T>G		intron_variant		1		ENSP00000425142
MLIP	ENST00000274897.9	c.64-15927T>G		intron_variant		2		ENSP00000274897	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59333 AN: 151952 Hom.: 12065 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.391 AC: 59431 AN: 152070 Hom.: 12102 Cov.: 32 AF XY: 0.386 AC XY: 28666 AN XY: 74348

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.378

Alfa AF: 0.383 Hom.: 1928

Bravo AF: 0.411

Asia WGS AF: 0.303 AC: 1056 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	0.17
DANN	Benign	0.49

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: rs545829; hg19: chr6-53970318;