chr20-37138813-C-T

Variant names:

• chr20-37138813-C-T
• rs1744767
• ENST00000343811.10:c.1489-843G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152503.8(MROH8):​c.1489-843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,816 control chromosomes in the GnomAD database, including 12,000 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 0.39 (12000 hom., cov: 31)
• Consequence: MROH8 NM_152503.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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

Verdict is Benign. Variant got -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 = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH8	NM_152503.8	c.1489-843G>A		intron_variant	Intron 12 of 24		NP_689716.4
MROH8	NM_213631.3	c.1489-843G>A		intron_variant	Intron 12 of 13		NP_998796.1
MROH8	NM_213632.3	c.1384-843G>A		intron_variant	Intron 11 of 12		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.1489-843G>A		intron_variant	Intron 12 of 24	1		ENSP00000513568.1
MROH8	ENST00000400440.7	c.1489-843G>A		intron_variant	Intron 12 of 13	1		ENSP00000513569.1
MROH8	ENST00000422138.2	c.1231-843G>A		intron_variant	Intron 10 of 22	3		ENSP00000400468.2
MROH8	ENST00000421643.2	c.1384-843G>A		intron_variant	Intron 11 of 12	2		ENSP00000513570.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59408 AN: 151698 Hom.: 11996 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.392 AC: 59441 AN: 151816 Hom.: 12000 Cov.: 31 AF XY: 0.392 AC XY: 29064 AN XY: 74132

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.413

Alfa AF: 0.424 Hom.: 21909

Bravo AF: 0.397

Asia WGS AF: 0.486 AC: 1688 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	7.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1744767; hg19: chr20-35767216;