rs3765018

chr1-54702625-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001039464.4(MROH7):c.3444G>A(p.Lys1148=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,605,828 control chromosomes in the GnomAD database, including 1,545 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.029 (242 hom., cov: 32)
  • Exomes 𝑓: 0.013 (1303 hom.)
• Consequence: MROH7 NM_001039464.4 splice_region, synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-54702625-G-A is Benign according to our data. Variant chr1-54702625-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.383 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH7	NM_001039464.4	c.3444G>A	p.Lys1148=	splice_region_variant, synonymous_variant	21/24	ENST00000421030.7
MROH7-TTC4	NR_037639.2	n.3978G>A		splice_region_variant, non_coding_transcript_exon_variant	22/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH7	ENST00000421030.7	c.3444G>A	p.Lys1148=	splice_region_variant, synonymous_variant	21/24	2	NM_001039464.4	P2

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4425 AN: 152136 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.0314 AC: 7706 AN: 245746 Hom.: 592 AF XY: 0.0314 AC XY: 4188 AN XY: 133422

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.0728

Gnomad FIN exome AF: 0.0000929

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.0133 AC: 19402 AN: 1453576 Hom.: 1303 Cov.: 31 AF XY: 0.0148 AC XY: 10672 AN XY: 723002

Gnomad4 AFR exome AF: 0.0679

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.0722

Gnomad4 FIN exome AF: 0.0000940

Gnomad4 NFE exome AF: 0.000603

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0293 AC: 4457 AN: 152252 Hom.: 242 Cov.: 32 AF XY: 0.0312 AC XY: 2324 AN XY: 74432

Gnomad4 AFR AF: 0.0628

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.00845 Hom.: 149

Bravo AF: 0.0309

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.66
Dann	Benign	0.46

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: rs3765018; hg19: chr1-55168298; COSMIC: COSV59868113; COSMIC: COSV59868113;