rs7784447

Variant names:

• chr7-114989231-G-A
• rs7784447
• NM_001166345.3:c.493+9450G>A

Variant summary

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

The NM_001166345.3(MDFIC):​c.493+9450G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,010 control chromosomes in the GnomAD database, including 6,255 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 0.28 (6255 hom., cov: 31)
• Consequence: MDFIC NM_001166345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 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.493+9450G>A		intron	N/A	NP_001159817.1	Q9P1T7-2
	MDFIC	NM_199072.5		c.820+9450G>A		intron	N/A	NP_951038.1	Q9P1T7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDFIC	ENST00000393486.6	TSL:1 MANE Select	c.493+9450G>A		intron	N/A	ENSP00000377126.1	Q9P1T7-2
	MDFIC	ENST00000963682.1		c.493+9450G>A		intron	N/A	ENSP00000633741.1
	MDFIC	ENST00000904588.1		c.493+9450G>A		intron	N/A	ENSP00000574647.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42712 AN: 151894 Hom.: 6241 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.281 AC: 42752 AN: 152010 Hom.: 6255 Cov.: 31 AF XY: 0.275 AC XY: 20416 AN XY: 74292

African (AFR) AF: 0.255 AC: 10566 AN: 41462

American (AMR) AF: 0.287 AC: 4376 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3464

East Asian (EAS) AF: 0.0598 AC: 309 AN: 5166

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4820

European-Finnish (FIN) AF: 0.247 AC: 2612 AN: 10568

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21515 AN: 67950

Other (OTH) AF: 0.304 AC: 641 AN: 2110

Alfa AF: 0.305 Hom.: 32368

Bravo AF: 0.284

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.93
DANN	Benign	0.24
PhyloP100		0.016
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: rs7784447; hg19: chr7-114629285;