rs75269200

chr1-54678793-A-G

Variant summary

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

The NM_001039464.4(MROH7):c.1988A>G(p.Lys663Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,080 control chromosomes in the GnomAD database, including 703 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (219 hom., cov: 32)
  • Exomes 𝑓: 0.011 (484 hom.)
• Consequence: MROH7 NM_001039464.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

Genes affected

MROH7 (HGNC:24802): (maestro heat like repeat family member 7) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MROH7-TTC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025929213).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH7	NM_001039464.4	c.1988A>G	p.Lys663Arg	missense_variant	11/24	ENST00000421030.7
MROH7-TTC4	NR_037639.2	n.2522A>G		non_coding_transcript_exon_variant	12/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH7	ENST00000421030.7	c.1988A>G	p.Lys663Arg	missense_variant	11/24	2	NM_001039464.4	P2

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5262 AN: 152138 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0233 AC: 5823 AN: 249570 Hom.: 188 AF XY: 0.0227 AC XY: 3073 AN XY: 135402

Gnomad AFR exome AF: 0.0883

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0184

Gnomad EAS exome AF: 0.0693

Gnomad SAS exome AF: 0.0457

Gnomad FIN exome AF: 0.0388

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0105 AC: 15414 AN: 1461824 Hom.: 484 Cov.: 31 AF XY: 0.0112 AC XY: 8142 AN XY: 727216

Gnomad4 AFR exome AF: 0.0908

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.0821

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.00123

Gnomad4 OTH exome AF: 0.0163

GnomAD4 genome AF: 0.0348 AC: 5293 AN: 152256 Hom.: 219 Cov.: 32 AF XY: 0.0369 AC XY: 2747 AN XY: 74458

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.0665

Gnomad4 SAS AF: 0.0578

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0107 Hom.: 99

Bravo AF: 0.0339

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0767 AC: 302

ESP6500EA AF: 0.00290 AC: 24

ExAC AF: 0.0250 AC: 3019

Asia WGS AF: 0.0870 AC: 300 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	-0.0099
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.60	T;T;T;T
MetaRNN	Benign	0.0026	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationTaster	Benign	0.88	N;N;N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.87	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.93	P;B;.;.
Vest4		0.14
MPC		0.29
ClinPred		0.025	T
GERP RS		3.9
Varity_R		0.074
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs75269200; hg19: chr1-55144466; COSMIC: COSV59868097;