rs13247874

chr7-73596112-C-T

Variant summary

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

The NM_032951.3(MLXIPL):c.2058+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,605,758 control chromosomes in the GnomAD database, including 26,324 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 (1864 hom., cov: 30)
  • Exomes 𝑓: 0.18 (24460 hom.)
• Consequence: MLXIPL NM_032951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MLXIPL	NM_032951.3	c.2058+41G>A		intron_variant		ENST00000313375.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MLXIPL	ENST00000313375.8	c.2058+41G>A		intron_variant		1	NM_032951.3	A2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22610 AN: 151770 Hom.: 1863 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.0999

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.148 AC: 35583 AN: 240544 Hom.: 2933 AF XY: 0.149 AC XY: 19638 AN XY: 131618

Gnomad AFR exome AF: 0.0959

Gnomad AMR exome AF: 0.0915

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.0930

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.179 AC: 260122 AN: 1453870 Hom.: 24460 Cov.: 36 AF XY: 0.177 AC XY: 127888 AN XY: 722812

Gnomad4 AFR exome AF: 0.0970

Gnomad4 AMR exome AF: 0.0938

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.0958

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.149 AC: 22622 AN: 151888 Hom.: 1864 Cov.: 30 AF XY: 0.147 AC XY: 10914 AN XY: 74210

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.149

Alfa AF: 0.167 Hom.: 423

Bravo AF: 0.143

Asia WGS AF: 0.110 AC: 384 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.4
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13247874; hg19: chr7-73010442; COSMIC: COSV57670033; COSMIC: COSV57670033;