rs17625497

Variant names:

• chr6-54019045-G-A
• rs17625497
• ENST00000514921.5:c.17G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-54019045-G-A
• chr6-54019045-G-T

Variant summary

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

The ENST00000514921.5(MLIP):​c.17G>A​(p.Arg6His) variant causes a missense change. The variant allele was found at a frequency of 0.258 in 1,606,772 control chromosomes in the GnomAD database, including 56,579 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5203 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51376 hom.)
• Consequence: MLIP ENST00000514921.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 18 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 (MetaRNN=0.0018709004).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281746.2	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 12		NP_001268675.1
MLIP	NM_138569.3	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 13		NP_612636.2
MLIP	XM_005249476.6	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 14		XP_005249533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000514921.5	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 12	1		ENSP00000425142.1
MLIP	ENST00000274897.9	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 13	2		ENSP00000274897.5
MLIP	ENST00000370877.6	c.17G>A	p.Arg6His	missense_variant	Exon 1 of 8	5		ENSP00000359914.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38183 AN: 151756 Hom.: 5203 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.260 AC: 64894 AN: 249472 AF XY: 0.254

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.0574

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.259 AC: 376968 AN: 1454900 Hom.: 51376 Cov.: 31 AF XY: 0.257 AC XY: 185866 AN XY: 724046

African (AFR) AF: 0.185 AC: 6134 AN: 33242

American (AMR) AF: 0.406 AC: 18024 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6853 AN: 26040

East Asian (EAS) AF: 0.0796 AC: 3155 AN: 39640

South Asian (SAS) AF: 0.182 AC: 15610 AN: 85806

European-Finnish (FIN) AF: 0.283 AC: 15113 AN: 53340

Middle Eastern (MID) AF: 0.293 AC: 1680 AN: 5736

European-Non Finnish (NFE) AF: 0.267 AC: 295262 AN: 1106636

Other (OTH) AF: 0.252 AC: 15137 AN: 60114

GnomAD4 genome AF: 0.252 AC: 38200 AN: 151872 Hom.: 5203 Cov.: 32 AF XY: 0.252 AC XY: 18740 AN XY: 74222

African (AFR) AF: 0.190 AC: 7871 AN: 41416

American (AMR) AF: 0.385 AC: 5856 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3464

East Asian (EAS) AF: 0.0626 AC: 324 AN: 5176

South Asian (SAS) AF: 0.165 AC: 790 AN: 4794

European-Finnish (FIN) AF: 0.287 AC: 3024 AN: 10548

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18377 AN: 67930

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.267 Hom.: 22697

Bravo AF: 0.260

TwinsUK AF: 0.261 AC: 966

ALSPAC AF: 0.262 AC: 1008

ESP6500AA AF: 0.182 AC: 804

ESP6500EA AF: 0.281 AC: 2418

ExAC AF: 0.252 AC: 30648

Asia WGS AF: 0.152 AC: 529 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Benign	0.0029	.;T;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.59	T;T;T;T
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.90	N;N;.;.
PhyloP100		3.8
PROVEAN	Benign	1.8	N;N;N;N
REVEL	Benign	0.092
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.097
MPC		0.011
ClinPred		0.021	T
GERP RS		3.5
PromoterAI		-0.022	Neutral
Varity_R		0.031
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17625497; hg19: chr6-53883843; COSMIC: COSV51430561; COSMIC: COSV51430561;