20-37144941-C-T

Variant names:

• chr20-37144941-C-T
• rs1780682
• ENST00000343811.10:c.1211-1100G>A

Variant summary

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

The ENST00000343811.10(MROH8):​c.1211-1100G>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 152,140 control chromosomes in the GnomAD database, including 12,032 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 (12032 hom., cov: 33)
• Consequence: MROH8 ENST00000343811.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 6 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=-0.92).
• 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.1211-1100G>A		intron_variant	Intron 10 of 24		NP_689716.4
MROH8	NM_213631.3	c.1211-1100G>A		intron_variant	Intron 10 of 13		NP_998796.1
MROH8	NM_213632.3	c.1106-1100G>A		intron_variant	Intron 9 of 12		NP_998797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH8	ENST00000343811.10	c.1211-1100G>A		intron_variant	Intron 10 of 24	1		ENSP00000513568.1
MROH8	ENST00000400440.7	c.1211-1100G>A		intron_variant	Intron 10 of 13	1		ENSP00000513569.1
MROH8	ENST00000422138.2	c.1106-1100G>A		intron_variant	Intron 9 of 22	3		ENSP00000400468.2
MROH8	ENST00000421643.2	c.1106-1100G>A		intron_variant	Intron 9 of 12	2		ENSP00000513570.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59544 AN: 152022 Hom.: 12028 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.392 AC: 59577 AN: 152140 Hom.: 12032 Cov.: 33 AF XY: 0.392 AC XY: 29165 AN XY: 74362

African (AFR) AF: 0.296 AC: 12309 AN: 41522

American (AMR) AF: 0.491 AC: 7503 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2483 AN: 5178

South Asian (SAS) AF: 0.467 AC: 2258 AN: 4832

European-Finnish (FIN) AF: 0.326 AC: 3447 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28644 AN: 67978

Other (OTH) AF: 0.415 AC: 874 AN: 2108

Alfa AF: 0.417 Hom.: 8757

Bravo AF: 0.397

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.068
DANN	Benign	0.62
PhyloP100		-2.1
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: rs1780682; hg19: chr20-35773344;