chr7-73593613-G-A

Variant names:

• chr7-73593613-G-A
• rs1051921
• NM_032951.3:c.*252C>T

Variant summary

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

The NM_032951.3(MLXIPL):​c.*252C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 475,522 control chromosomes in the GnomAD database, including 6,387 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 (1858 hom., cov: 31)
  • Exomes 𝑓: 0.16 (4529 hom.)
• Consequence: MLXIPL NM_032951.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 28 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 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.*252C>T		3_prime_UTR	Exon 17 of 17	NP_116569.1	Q9NP71-1
	MLXIPL	NM_032953.3		c.*252C>T		3_prime_UTR	Exon 17 of 17	NP_116571.1	Q9NP71-3
	MLXIPL	NM_032952.3		c.*252C>T		3_prime_UTR	Exon 17 of 17	NP_116570.1	Q9NP71-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLXIPL	ENST00000313375.8	TSL:1 MANE Select	c.*252C>T		3_prime_UTR	Exon 17 of 17	ENSP00000320886.3	Q9NP71-1
	MLXIPL	ENST00000414749.6	TSL:1	c.*252C>T		3_prime_UTR	Exon 17 of 17	ENSP00000412330.2	Q9NP71-3
	MLXIPL	ENST00000429400.6	TSL:1	c.*252C>T		3_prime_UTR	Exon 17 of 17	ENSP00000406296.2	Q9NP71-2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22579 AN: 151996 Hom.: 1857 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0982

Gnomad SAS AF: 0.0998

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.159 AC: 51500 AN: 323410 Hom.: 4529 Cov.: 0 AF XY: 0.155 AC XY: 26681 AN XY: 171766

African (AFR) AF: 0.0944 AC: 881 AN: 9334

American (AMR) AF: 0.105 AC: 1566 AN: 14846

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 1586 AN: 9614

East Asian (EAS) AF: 0.0936 AC: 1837 AN: 19618

South Asian (SAS) AF: 0.104 AC: 4559 AN: 43764

European-Finnish (FIN) AF: 0.173 AC: 3126 AN: 18104

Middle Eastern (MID) AF: 0.144 AC: 190 AN: 1316

European-Non Finnish (NFE) AF: 0.185 AC: 34889 AN: 188718

Other (OTH) AF: 0.158 AC: 2866 AN: 18096

GnomAD4 genome AF: 0.149 AC: 22590 AN: 152112 Hom.: 1858 Cov.: 31 AF XY: 0.147 AC XY: 10905 AN XY: 74358

African (AFR) AF: 0.100 AC: 4167 AN: 41490

American (AMR) AF: 0.116 AC: 1776 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3468

East Asian (EAS) AF: 0.0986 AC: 511 AN: 5180

South Asian (SAS) AF: 0.100 AC: 481 AN: 4808

European-Finnish (FIN) AF: 0.160 AC: 1692 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12894 AN: 67982

Other (OTH) AF: 0.146 AC: 308 AN: 2110

Alfa AF: 0.166 Hom.: 2359

Bravo AF: 0.142

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.0
DANN	Benign	0.86
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1051921; hg19: chr7-73007943;