1-54653616-G-C

Variant names:

• chr1-54653616-G-C
• rs9332417
• NM_001039464.4:c.690G>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001039464.4(MROH7):​c.690G>C​(p.Leu230Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,613,626 control chromosomes in the GnomAD database, including 250,435 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 0.49 (19575 hom., cov: 31)
  • Exomes 𝑓: 0.56 (230860 hom.)
• Consequence: MROH7 NM_001039464.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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:49180): (MROH7-TTC4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MROH7 (maestro heat-like repeat family member 7) and TTC4 (tetratricopeptide repeat domain 4) genes. Alternative splicing results in multiple transcript variants, which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to produce protein products. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH7	NM_001039464.4	c.690G>C	p.Leu230Leu	synonymous_variant	Exon 3 of 24	ENST00000421030.7	NP_001034553.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH7	ENST00000421030.7	c.690G>C	p.Leu230Leu	synonymous_variant	Exon 3 of 24	2	NM_001039464.4	ENSP00000396622.2
MROH7-TTC4	ENST00000414150.6	n.690G>C		non_coding_transcript_exon_variant	Exon 3 of 33	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74979 AN: 151776 Hom.: 19576 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.514

GnomAD3 exomes AF: 0.505 AC: 125809 AN: 249122 Hom.: 33455 AF XY: 0.507 AC XY: 68548 AN XY: 135176

Gnomad AFR exome AF: 0.319

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.524

Gnomad EAS exome AF: 0.536

Gnomad SAS exome AF: 0.373

Gnomad FIN exome AF: 0.593

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.557 AC: 814001 AN: 1461732 Hom.: 230860 Cov.: 70 AF XY: 0.552 AC XY: 401490 AN XY: 727176

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.525

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.592

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.494 AC: 74980 AN: 151894 Hom.: 19575 Cov.: 31 AF XY: 0.491 AC XY: 36399 AN XY: 74206

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.509

Alfa AF: 0.557 Hom.: 7814

Bravo AF: 0.478

Asia WGS AF: 0.408 AC: 1419 AN: 3478

EpiCase AF: 0.587

EpiControl AF: 0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.67

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: rs9332417; hg19: chr1-55119289; COSMIC: COSV59869425; COSMIC: COSV59869425;