chr5-40998094-T-C

Position:

• chr5-40998094-T-C

Variant summary

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

The NM_173489.5(MROH2B):​c.4716A>G​(p.Gln1572Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 1,605,046 control chromosomes in the GnomAD database, including 338,323 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 0.64 (31214 hom., cov: 33)
  • Exomes 𝑓: 0.65 (307109 hom.)
• Consequence: MROH2B NM_173489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MROH2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.4716A>G	p.Gln1572Gln	synonymous_variant	42/42	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513953.2	c.4530A>G	p.Gln1510Gln	synonymous_variant	41/41		XP_011512255.1
MROH2B	XM_011513952.2	c.*81A>G		3_prime_UTR_variant	43/43		XP_011512254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.4716A>G	p.Gln1572Gln	synonymous_variant	42/42	1	NM_173489.5	ENSP00000382476.4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97071 AN: 151980 Hom.: 31192 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.634 AC: 156568 AN: 246822 Hom.: 50265 AF XY: 0.630 AC XY: 84302 AN XY: 133896

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.699

Gnomad SAS exome AF: 0.538

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.648 AC: 941316 AN: 1452948 Hom.: 307109 Cov.: 36 AF XY: 0.645 AC XY: 465956 AN XY: 722954

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.603

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.720

Gnomad4 NFE exome AF: 0.657

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.639 AC: 97147 AN: 152098 Hom.: 31214 Cov.: 33 AF XY: 0.638 AC XY: 47438 AN XY: 74380

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.620

Alfa AF: 0.647 Hom.: 62088

Bravo AF: 0.629

Asia WGS AF: 0.621 AC: 2158 AN: 3478

EpiCase AF: 0.649

EpiControl AF: 0.640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.2
DANN	Benign	0.69

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: rs704040; hg19: chr5-40998196; COSMIC: COSV68183320;