rs7798357

Variant names:

• chr7-73617935-G-C
• rs7798357
• NM_032951.3:c.294-1758C>G

Variant summary

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

The NM_032951.3(MLXIPL):​c.294-1758C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,054 control chromosomes in the GnomAD database, including 5,984 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 0.27 (5984 hom., cov: 31)
• Consequence: MLXIPL NM_032951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLXIPL	NM_032951.3	MANE Select	c.294-1758C>G		intron	N/A	NP_116569.1
	MLXIPL	NM_032953.3		c.294-1758C>G		intron	N/A	NP_116571.1
	MLXIPL	NM_032952.3		c.294-1758C>G		intron	N/A	NP_116570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLXIPL	ENST00000313375.8	TSL:1 MANE Select	c.294-1758C>G		intron	N/A	ENSP00000320886.3
	MLXIPL	ENST00000414749.6	TSL:1	c.294-1758C>G		intron	N/A	ENSP00000412330.2
	MLXIPL	ENST00000429400.6	TSL:1	c.294-1758C>G		intron	N/A	ENSP00000406296.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41554 AN: 151936 Hom.: 5963 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.274 AC: 41614 AN: 152054 Hom.: 5984 Cov.: 31 AF XY: 0.269 AC XY: 19956 AN XY: 74304

African (AFR) AF: 0.346 AC: 14355 AN: 41450

American (AMR) AF: 0.201 AC: 3079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3470

East Asian (EAS) AF: 0.110 AC: 567 AN: 5156

South Asian (SAS) AF: 0.172 AC: 828 AN: 4820

European-Finnish (FIN) AF: 0.212 AC: 2238 AN: 10576

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18928 AN: 67984

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.278 Hom.: 732

Bravo AF: 0.276

Asia WGS AF: 0.170 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		-0.34
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: rs7798357; hg19: chr7-73032265;