7-73612048-C-T

Variant names:

• chr7-73612048-C-T
• rs17145750
• NM_032951.3:c.400+4023G>A

Variant summary

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

The NM_032951.3(MLXIPL):​c.400+4023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 151,550 control chromosomes in the GnomAD database, including 1,385 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 0.13 (1385 hom., cov: 31)
• Consequence: MLXIPL NM_032951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 58 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLXIPL	NM_032951.3	c.400+4023G>A		intron_variant	Intron 2 of 16	ENST00000313375.8	NP_116569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLXIPL	ENST00000313375.8	c.400+4023G>A		intron_variant	Intron 2 of 16	1	NM_032951.3	ENSP00000320886.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20113 AN: 151430 Hom.: 1383 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.133 AC: 20122 AN: 151550 Hom.: 1385 Cov.: 31 AF XY: 0.132 AC XY: 9758 AN XY: 74070

African (AFR) AF: 0.110 AC: 4525 AN: 41290

American (AMR) AF: 0.102 AC: 1551 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.111 AC: 566 AN: 5092

South Asian (SAS) AF: 0.0927 AC: 445 AN: 4798

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10572

Middle Eastern (MID) AF: 0.135 AC: 39 AN: 288

European-Non Finnish (NFE) AF: 0.156 AC: 10608 AN: 67840

Other (OTH) AF: 0.124 AC: 261 AN: 2104

Alfa AF: 0.143 Hom.: 6230

Bravo AF: 0.127

Asia WGS AF: 0.116 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.62
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17145750; hg19: chr7-73026378;