chr8-97679242-A-G

Variant names:

• chr8-97679242-A-G
• rs2438224
• NM_178812.4:c.484-7426A>G

Variant summary

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

The NM_178812.4(MTDH):​c.484-7426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,230 control chromosomes in the GnomAD database, including 929 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 0.093 (929 hom., cov: 31)
• Consequence: MTDH NM_178812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 2 publications found

Genes affected

MTDH (HGNC:29608): (metadherin) Enables NF-kappaB binding activity; double-stranded RNA binding activity; and transcription coactivator activity. Involved in several processes, including lipopolysaccharide-mediated signaling pathway; positive regulation of intracellular signal transduction; and regulation of transcription, DNA-templated. Located in endoplasmic reticulum; nuclear lumen; and perinuclear region of cytoplasm. Implicated in hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTDH	NM_178812.4	MANE Select	c.484-7426A>G		intron	N/A	NP_848927.2
	MTDH	NM_001363137.1		c.484-7426A>G		intron	N/A	NP_001350066.1
	MTDH	NM_001363136.1		c.484-7426A>G		intron	N/A	NP_001350065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTDH	ENST00000336273.8	TSL:1 MANE Select	c.484-7426A>G		intron	N/A	ENSP00000338235.3
	MTDH	ENST00000519934.5	TSL:5	c.415-7426A>G		intron	N/A	ENSP00000428168.1
	MTDH	ENST00000522313.1	TSL:4	c.196-7426A>G		intron	N/A	ENSP00000428703.1

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14216 AN: 152112 Hom.: 923 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0935 AC: 14228 AN: 152230 Hom.: 929 Cov.: 31 AF XY: 0.0991 AC XY: 7373 AN XY: 74422

African (AFR) AF: 0.0716 AC: 2974 AN: 41550

American (AMR) AF: 0.193 AC: 2945 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 306 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1279 AN: 5186

South Asian (SAS) AF: 0.163 AC: 784 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4565 AN: 68014

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0424 Hom.: 46

Bravo AF: 0.0987

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.098
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: rs2438224; hg19: chr8-98691470;