chr6-54059899-T-C

Variant names:

• chr6-54059899-T-C
• rs9296736
• ENST00000514921.5:c.63+40808T>C

Variant summary

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

The NM_001281746.2(MLIP):​c.63+40808T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,088 control chromosomes in the GnomAD database, including 23,869 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 0.51 (23869 hom., cov: 44)
• Consequence: MLIP NM_001281746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 23 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-AS1 (HGNC:40963): (MLIP antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281746.2. 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
	MLIP	NM_001281746.2		c.63+40808T>C		intron	N/A	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.63+40808T>C		intron	N/A	NP_612636.2	Q5VWP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000514921.5	TSL:1	c.63+40808T>C		intron	N/A	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000274897.9	TSL:2	c.63+40808T>C		intron	N/A	ENSP00000274897.5	Q5VWP3-1
	MLIP	ENST00000370877.6	TSL:5	c.63+40808T>C		intron	N/A	ENSP00000359914.2	E2QRH6

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77891 AN: 151970 Hom.: 23875 Cov.: 44

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.512 AC: 77887 AN: 152088 Hom.: 23869 Cov.: 44 AF XY: 0.514 AC XY: 38220 AN XY: 74362

African (AFR) AF: 0.165 AC: 6845 AN: 41476

American (AMR) AF: 0.482 AC: 7363 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3472

East Asian (EAS) AF: 0.487 AC: 2520 AN: 5176

South Asian (SAS) AF: 0.577 AC: 2785 AN: 4826

European-Finnish (FIN) AF: 0.700 AC: 7420 AN: 10602

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46768 AN: 67952

Other (OTH) AF: 0.548 AC: 1157 AN: 2112

Alfa AF: 0.604 Hom.: 27668

Bravo AF: 0.480

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		0.13
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: rs9296736; hg19: chr6-53924697;