chr7-157009230-G-A

Position:

• chr7-157009230-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000252971.11(MNX1):​c.691+430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,434,696 control chromosomes in the GnomAD database, including 8,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2211 hom., cov: 33)
  • Exomes 𝑓: 0.090 (6138 hom.)
• Consequence: MNX1 ENST00000252971.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.109

Genes affected

MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-157009230-G-A is Benign according to our data. Variant chr7-157009230-G-A is described in ClinVar as [Benign]. Clinvar id is 1293974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNX1	NM_005515.4	c.691+430C>T		intron_variant		ENST00000252971.11	NP_005506.3
MNX1	NM_001165255.2	c.-178C>T		5_prime_UTR_variant	1/3		NP_001158727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNX1	ENST00000252971.11	c.691+430C>T		intron_variant		1	NM_005515.4	ENSP00000252971	P2

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21796 AN: 152150 Hom.: 2202 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0897 AC: 115084 AN: 1282428 Hom.: 6138 Cov.: 31 AF XY: 0.0878 AC XY: 54553 AN XY: 621598

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0896

Gnomad4 OTH exome AF: 0.0928

GnomAD4 genome AF: 0.143 AC: 21836 AN: 152268 Hom.: 2211 Cov.: 33 AF XY: 0.140 AC XY: 10424 AN XY: 74462

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0640

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.149

Alfa AF: 0.112 Hom.: 319

Bravo AF: 0.155

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6979196; hg19: chr7-156801924;