7-114956786-T-G

Variant names:

• chr7-114956786-T-G
• rs2709505
• NM_001166345.3:c.217+14389T>G

Variant summary

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

The NM_001166345.3(MDFIC):​c.217+14389T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,164 control chromosomes in the GnomAD database, including 1,313 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 0.11 (1313 hom., cov: 31)
• Consequence: MDFIC NM_001166345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 4 publications found

Genes affected

MDFIC (HGNC:28870): (MyoD family inhibitor domain containing) This gene product is a member of a family of proteins characterized by a specific cysteine-rich C-terminal domain, which is involved in transcriptional regulation of viral genome expression. Alternative translation initiation from an upstream non-AUG (GUG), and an in-frame, downstream AUG codon, results in the production of two isoforms, p40 and p32, respectively, which have different subcellular localization; p32 is mainly found in the cytoplasm, whereas p40 is targeted to the nucleolus. Both isoforms have transcriptional regulatory activity that is attributable to the cysteine-rich C-terminal domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MDFIC Gene-Disease associations (from GenCC):

• lymphatic malformation 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166345.3. 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
	MDFIC	NM_001166345.3	MANE Select	c.217+14389T>G		intron	N/A	NP_001159817.1
	MDFIC	NM_199072.5		c.544+14389T>G		intron	N/A	NP_951038.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDFIC	ENST00000393486.6	TSL:1 MANE Select	c.217+14389T>G		intron	N/A	ENSP00000377126.1
	MDFIC	ENST00000963682.1		c.217+14389T>G		intron	N/A	ENSP00000633741.1
	MDFIC	ENST00000904588.1		c.217+14389T>G		intron	N/A	ENSP00000574647.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16421 AN: 152046 Hom.: 1308 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.108 AC: 16453 AN: 152164 Hom.: 1313 Cov.: 31 AF XY: 0.105 AC XY: 7845 AN XY: 74394

African (AFR) AF: 0.226 AC: 9361 AN: 41472

American (AMR) AF: 0.0748 AC: 1142 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.102 AC: 491 AN: 4822

European-Finnish (FIN) AF: 0.0223 AC: 237 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4609 AN: 68010

Other (OTH) AF: 0.112 AC: 238 AN: 2116

Alfa AF: 0.0799 Hom.: 1181

Bravo AF: 0.116

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		0.24
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: rs2709505; hg19: chr7-114596841;