rs644955

Variant names:

• chr1-54702411-C-T
• rs644955
• NM_001039464.4:c.3441+166C>T

Variant summary

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

The NM_001039464.4(MROH7):​c.3441+166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,986 control chromosomes in the GnomAD database, including 25,033 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 0.57 (25033 hom., cov: 32)
• Consequence: MROH7 NM_001039464.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.908
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039464.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	NM_001039464.4	MANE Select	c.3441+166C>T		intron	N/A	NP_001034553.3	Q68CQ1-7
	MROH7	NM_001291332.2		c.1995+166C>T		intron	N/A	NP_001278261.1
	MROH7	NR_026782.3		n.3743+166C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH7	ENST00000421030.7	TSL:2 MANE Select	c.3441+166C>T		intron	N/A	ENSP00000396622.2	Q68CQ1-7
	MROH7-TTC4	ENST00000414150.6	TSL:2	n.3441+166C>T		intron	N/A	ENSP00000410192.2	A0A0A0MT08
	MROH7	ENST00000422659.5	TSL:1	n.*1573+166C>T		intron	N/A	ENSP00000388181.1	Q68CQ1-8

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85812 AN: 151868 Hom.: 24997 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.565 AC: 85913 AN: 151986 Hom.: 25033 Cov.: 32 AF XY: 0.570 AC XY: 42318 AN XY: 74298

African (AFR) AF: 0.690 AC: 28610 AN: 41458

American (AMR) AF: 0.559 AC: 8541 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1730 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3919 AN: 5166

South Asian (SAS) AF: 0.629 AC: 3021 AN: 4802

European-Finnish (FIN) AF: 0.508 AC: 5361 AN: 10548

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32900 AN: 67952

Other (OTH) AF: 0.551 AC: 1165 AN: 2114

Alfa AF: 0.508 Hom.: 33259

Bravo AF: 0.573

Asia WGS AF: 0.660 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.66
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs644955; hg19: chr1-55168084; COSMIC: COSV59869903; COSMIC: COSV59869903;