rs248247

Positions:

• chr5-179840783-G-A

Variant summary

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

The ENST00000292586.11(MRNIP):​c.537+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 999,016 control chromosomes in the GnomAD database, including 63,339 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 0.32 (8241 hom., cov: 33)
  • Exomes 𝑓: 0.35 (55098 hom.)
• Consequence: MRNIP ENST00000292586.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

MRNIP (HGNC:30817): (MRN complex interacting protein) Enables chromatin binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of double-strand break repair; and response to ionizing radiation. Located in nucleoplasm. Colocalizes with Mre11 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRNIP	NM_016175.4	c.537+89C>T		intron_variant		ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3	c.372+89C>T		intron_variant			NP_001017987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11	c.537+89C>T		intron_variant		1	NM_016175.4	ENSP00000292586	P2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48011 AN: 151676 Hom.: 8235 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.354 AC: 52209 AN: 147398 Hom.: 9819 AF XY: 0.360 AC XY: 28118 AN XY: 78090

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.481

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.355 AC: 300749 AN: 847222 Hom.: 55098 Cov.: 11 AF XY: 0.358 AC XY: 155884 AN XY: 435756

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.316 AC: 48030 AN: 151794 Hom.: 8241 Cov.: 33 AF XY: 0.325 AC XY: 24076 AN XY: 74178

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.295

Alfa AF: 0.338 Hom.: 12268

Bravo AF: 0.290

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs248247; hg19: chr5-179267783; COSMIC: COSV52976373; COSMIC: COSV52976373;