ENST00000319836.7:c.-79+13448C>T

Variant names:

• chr10-45580787-G-A
• rs7086046
• ENST00000319836.7:c.-79+13448C>T

Variant summary

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

The ENST00000319836.7(MARCHF8):​c.-79+13448C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,008 control chromosomes in the GnomAD database, including 4,159 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 0.23 (4159 hom., cov: 31)
• Consequence: MARCHF8 ENST00000319836.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 10 publications found

Genes affected

MARCHF8 (HGNC:23356): (membrane associated ring-CH-type finger 8) MARCH8 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Apr 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCHF8	XM_047424763.1	c.-188C>T		5_prime_UTR_variant	Exon 1 of 9		XP_047280719.1
MARCHF8	XM_047424766.1	c.-95C>T		5_prime_UTR_variant	Exon 1 of 8		XP_047280722.1
MARCHF8	XM_047424767.1	c.-188C>T		5_prime_UTR_variant	Exon 1 of 8		XP_047280723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCHF8	ENST00000319836.7	c.-79+13448C>T		intron_variant	Intron 1 of 6	1		ENSP00000317087.3
MARCHF8	ENST00000453980.3	c.-172+13448C>T		intron_variant	Intron 1 of 5	5		ENSP00000396678.1
MARCHF8	ENST00000602712.2	n.343+13448C>T		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34230 AN: 151888 Hom.: 4158 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.225 AC: 34227 AN: 152008 Hom.: 4159 Cov.: 31 AF XY: 0.228 AC XY: 16924 AN XY: 74300

African (AFR) AF: 0.161 AC: 6652 AN: 41442

American (AMR) AF: 0.290 AC: 4430 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3470

East Asian (EAS) AF: 0.0572 AC: 296 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4810

European-Finnish (FIN) AF: 0.289 AC: 3050 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17218 AN: 67964

Other (OTH) AF: 0.231 AC: 486 AN: 2106

Alfa AF: 0.248 Hom.: 8151

Bravo AF: 0.220

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		-0.34
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: rs7086046; hg19: chr10-46076235;