rs8120307

Variant names:

• chr20-37174785-T-C
• rs8120307
• ENST00000343811.10:c.258-669A>G

Variant summary

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

The ENST00000343811.10(MROH8):​c.258-669A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,978 control chromosomes in the GnomAD database, including 15,046 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 0.42 (15046 hom., cov: 32)
• Consequence: MROH8 ENST00000343811.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 3 publications found

Genes affected

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.258-669A>G		intron_variant	Intron 2 of 24		NP_689716.4
MROH8	NM_213631.3	c.258-669A>G		intron_variant	Intron 2 of 13		NP_998796.1
MROH8	NM_213632.3	c.258-669A>G		intron_variant	Intron 2 of 12		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.258-669A>G		intron_variant	Intron 2 of 24	1		ENSP00000513568.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64100 AN: 151860 Hom.: 15023 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.422 AC: 64160 AN: 151978 Hom.: 15046 Cov.: 32 AF XY: 0.413 AC XY: 30678 AN XY: 74292

African (AFR) AF: 0.616 AC: 25527 AN: 41444

American (AMR) AF: 0.298 AC: 4554 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3468

East Asian (EAS) AF: 0.0101 AC: 52 AN: 5158

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3564 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26479 AN: 67948

Other (OTH) AF: 0.422 AC: 887 AN: 2102

Alfa AF: 0.389 Hom.: 6290

Bravo AF: 0.428

Asia WGS AF: 0.180 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.47
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8120307; hg19: chr20-35803188;