rs13226650

Positions:

• chr7-73602675-A-G

Variant summary

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

The NM_032951.3(MLXIPL):​c.902-2980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,594 control chromosomes in the GnomAD database, including 2,685 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 0.18 (2685 hom., cov: 31)
• Consequence: MLXIPL NM_032951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLXIPL	NM_032951.3	c.902-2980T>C		intron_variant		ENST00000313375.8	NP_116569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLXIPL	ENST00000313375.8	c.902-2980T>C		intron_variant		1	NM_032951.3	ENSP00000320886	A2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27831 AN: 151478 Hom.: 2682 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.184 AC: 27854 AN: 151594 Hom.: 2685 Cov.: 31 AF XY: 0.181 AC XY: 13370 AN XY: 74030

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.165

Alfa AF: 0.185 Hom.: 4237

Bravo AF: 0.182

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.53

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: rs13226650; hg19: chr7-73017005;