rs1409104

chr6-54004652-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_046832.1(MLIP-IT1):n.461+1933C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,976 control chromosomes in the GnomAD database, including 14,720 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 0.43 (14720 hom., cov: 32)
• Consequence: MLIP-IT1 NR_046832.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

Genes affected

MLIP-AS1 (HGNC:40963): (MLIP antisense RNA 1)

MLIP-IT1 (HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLIP-IT1	NR_046832.1	n.461+1933C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLIP-AS1	ENST00000626804.2	n.194-25935G>A		intron_variant, non_coding_transcript_variant		5
MLIP	ENST00000505762.1	c.150+21802C>T		intron_variant		3
MLIP	ENST00000441845.2	n.525+1933C>T		intron_variant, non_coding_transcript_variant		2
MLIP-AS1	ENST00000626297.2	n.193-15500G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65170 AN: 151858 Hom.: 14725 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.429 AC: 65170 AN: 151976 Hom.: 14720 Cov.: 32 AF XY: 0.427 AC XY: 31678 AN XY: 74260

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.0867

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.435

Alfa AF: 0.457 Hom.: 2042

Bravo AF: 0.414

Asia WGS AF: 0.269 AC: 934 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	17
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1409104; hg19: chr6-53869450;