rs1051921

Positions:

• chr7-73593613-G-A

Variant summary

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

The NM_032951.3(MLXIPL):​c.*252C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 475,522 control chromosomes in the GnomAD database, including 6,387 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 0.15 (1858 hom., cov: 31)
  • Exomes 𝑓: 0.16 (4529 hom.)
• Consequence: MLXIPL NM_032951.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

Genes affected

MLXIPL (HGNC:12744): (MLX interacting protein like) This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIPL	NM_032951.3	c.*252C>T		3_prime_UTR_variant	17/17	ENST00000313375.8	NP_116569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLXIPL	ENST00000313375.8	c.*252C>T		3_prime_UTR_variant	17/17	1	NM_032951.3	ENSP00000320886	A2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22579 AN: 151996 Hom.: 1857 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.159 AC: 51500 AN: 323410 Hom.: 4529 Cov.: 0 AF XY: 0.155 AC XY: 26681 AN XY: 171766

Gnomad4 AFR exome AF: 0.0944

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0936

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.149 AC: 22590 AN: 152112 Hom.: 1858 Cov.: 31 AF XY: 0.147 AC XY: 10905 AN XY: 74358

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0986

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.146

Alfa AF: 0.172 Hom.: 1740

Bravo AF: 0.142

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.0
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1051921; hg19: chr7-73007943;