7-157006387-T-C

Variant names:

• chr7-157006387-T-C
• rs2270210
• NM_005515.4:c.852+92A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005515.4(MNX1):​c.852+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,412,262 control chromosomes in the GnomAD database, including 18,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (6325 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11771 hom.)
• Consequence: MNX1 NM_005515.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.19
• Publications: 5 publications found

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]

MNX1-AS2 (HGNC:40278): (MNX1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-157006387-T-C is Benign according to our data. Variant chr7-157006387-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005515.4. 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
	MNX1	NM_005515.4	MANE Select	c.852+92A>G		intron	N/A	NP_005506.3
	MNX1	NM_001165255.2		c.216+92A>G		intron	N/A	NP_001158727.1	P50219-2
	MNX1-AS2	NR_147077.1		n.81T>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	ENST00000252971.11	TSL:1 MANE Select	c.852+92A>G		intron	N/A	ENSP00000252971.5	P50219-1
	MNX1	ENST00000543409.5	TSL:1	c.216+92A>G		intron	N/A	ENSP00000438552.1	P50219-2
	MNX1	ENST00000428439.1	TSL:1	c.216+92A>G		intron	N/A	ENSP00000401158.1	C9K088

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34040 AN: 151874 Hom.: 6308 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.117 AC: 146891 AN: 1260270 Hom.: 11771 Cov.: 19 AF XY: 0.117 AC XY: 72583 AN XY: 620772

African (AFR) AF: 0.529 AC: 15409 AN: 29148

American (AMR) AF: 0.172 AC: 5369 AN: 31152

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 2149 AN: 21964

East Asian (EAS) AF: 0.121 AC: 4372 AN: 36148

South Asian (SAS) AF: 0.184 AC: 13336 AN: 72672

European-Finnish (FIN) AF: 0.0765 AC: 2909 AN: 38034

Middle Eastern (MID) AF: 0.144 AC: 544 AN: 3772

European-Non Finnish (NFE) AF: 0.0983 AC: 95778 AN: 974542

Other (OTH) AF: 0.133 AC: 7025 AN: 52838

GnomAD4 genome AF: 0.224 AC: 34095 AN: 151992 Hom.: 6325 Cov.: 32 AF XY: 0.222 AC XY: 16531 AN XY: 74310

African (AFR) AF: 0.514 AC: 21265 AN: 41408

American (AMR) AF: 0.190 AC: 2904 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.113 AC: 586 AN: 5164

South Asian (SAS) AF: 0.190 AC: 916 AN: 4818

European-Finnish (FIN) AF: 0.0698 AC: 738 AN: 10566

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6754 AN: 67970

Other (OTH) AF: 0.203 AC: 429 AN: 2116

Alfa AF: 0.138 Hom.: 3161

Bravo AF: 0.245

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.7
DANN	Benign	0.69
PhyloP100		-2.2
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: rs2270210; hg19: chr7-156799081;