7-114945750-C-T

Variant names:

• chr7-114945750-C-T
• rs2594458
• NM_001166345.3:c.217+3353C>T

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+3353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,252 control chromosomes in the GnomAD database, including 62,632 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 0.91 (62632 hom., cov: 33)
• Consequence: MDFIC NM_001166345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDFIC	NM_001166345.3	c.217+3353C>T		intron_variant	Intron 3 of 4	ENST00000393486.6	NP_001159817.1
MDFIC	NM_199072.5	c.544+3353C>T		intron_variant	Intron 3 of 4		NP_951038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486.6	c.217+3353C>T		intron_variant	Intron 3 of 4	1	NM_001166345.3	ENSP00000377126.1
MDFIC	ENST00000427207.5	c.175+3353C>T		intron_variant	Intron 2 of 3	3		ENSP00000392098.1
MDFIC	ENST00000498196.1	c.52+3353C>T		intron_variant	Intron 2 of 3	4		ENSP00000418337.1
MDFIC	ENST00000431629.5	n.187+3353C>T		intron_variant	Intron 2 of 4	5		ENSP00000416668.1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137749 AN: 152134 Hom.: 62584 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.905 AC: 137855 AN: 152252 Hom.: 62632 Cov.: 33 AF XY: 0.907 AC XY: 67546 AN XY: 74434

African (AFR) AF: 0.825 AC: 34239 AN: 41526

American (AMR) AF: 0.950 AC: 14532 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3205 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5187 AN: 5190

South Asian (SAS) AF: 0.935 AC: 4514 AN: 4830

European-Finnish (FIN) AF: 0.926 AC: 9805 AN: 10590

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63320 AN: 68026

Other (OTH) AF: 0.924 AC: 1951 AN: 2112

Alfa AF: 0.908 Hom.: 8132

Bravo AF: 0.904

Asia WGS AF: 0.964 AC: 3342 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.47
PhyloP100		-0.031
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: rs2594458; hg19: chr7-114585805;