rs2709505

Positions:

• chr7-114956786-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDFIC	NM_001166345.3	c.217+14389T>G		intron_variant		ENST00000393486.6	NP_001159817.1
MDFIC	NM_199072.5	c.544+14389T>G		intron_variant			NP_951038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDFIC	ENST00000393486.6	c.217+14389T>G		intron_variant		1	NM_001166345.3	ENSP00000377126	P1
MDFIC	ENST00000427207.5	c.175+14389T>G		intron_variant		3		ENSP00000392098
MDFIC	ENST00000498196.1	c.52+14389T>G		intron_variant		4		ENSP00000418337
MDFIC	ENST00000431629.5	c.187+14389T>G		intron_variant, NMD_transcript_variant		5		ENSP00000416668

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0896 Hom.: 251

Bravo AF: 0.116

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2709505; hg19: chr7-114596841;