chr7-73593276-T-C

Position:

• chr7-73593276-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032951.3(MLXIPL):​c.*589A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 171,104 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (177 hom., cov: 31)
  • Exomes 𝑓: 0.034 (28 hom.)
• Consequence: MLXIPL NM_032951.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.338

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]

MLXIPL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-73593276-T-C is Benign according to our data. Variant chr7-73593276-T-C is described in ClinVar as [Benign]. Clinvar id is 1277241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIPL	NM_032951.3	c.*589A>G		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	c.*589A>G		3_prime_UTR_variant	17/17	1	NM_032951.3	ENSP00000320886.3

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6470 AN: 146360 Hom.: 177 Cov.: 31

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0883

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0111

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0494

GnomAD4 exome AF: 0.0340 AC: 836 AN: 24622 Hom.: 28 Cov.: 0 AF XY: 0.0325 AC XY: 412 AN XY: 12696

Gnomad4 AFR exome AF: 0.00478

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00563

Gnomad4 FIN exome AF: 0.0361

Gnomad4 NFE exome AF: 0.0465

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0442 AC: 6468 AN: 146482 Hom.: 177 Cov.: 31 AF XY: 0.0425 AC XY: 3046 AN XY: 71588

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0271 Hom.: 18

Bravo AF: 0.0424

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	This variant is associated with the following publications: (PMID: 30079502) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.51

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: rs1051943; hg19: chr7-73007606;