rs2303677

Positions:

• chr5-179841779-C-T

Variant summary

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

The NM_016175.4(MRNIP):​c.449+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 990,722 control chromosomes in the GnomAD database, including 33,449 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 0.22 (4677 hom., cov: 32)
  • Exomes 𝑓: 0.24 (28772 hom.)
• Consequence: MRNIP NM_016175.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

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 = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRNIP	NM_016175.4	c.449+128G>A		intron_variant		ENST00000292586.11	NP_057259.2
MRNIP	NM_001017987.3	c.284+128G>A		intron_variant			NP_001017987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRNIP	ENST00000292586.11	c.449+128G>A		intron_variant		1	NM_016175.4	ENSP00000292586	P2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33367 AN: 152006 Hom.: 4671 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.244 AC: 204936 AN: 838598 Hom.: 28772 Cov.: 11 AF XY: 0.249 AC XY: 106978 AN XY: 429656

Gnomad4 AFR exome AF: 0.0880

Gnomad4 AMR exome AF: 0.488

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.219 AC: 33382 AN: 152124 Hom.: 4677 Cov.: 32 AF XY: 0.232 AC XY: 17217 AN XY: 74352

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.227

Alfa AF: 0.229 Hom.: 2385

Bravo AF: 0.219

Asia WGS AF: 0.423 AC: 1470 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	5.0
DANN	Benign	0.75

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: rs2303677; hg19: chr5-179268779; COSMIC: COSV52973905; COSMIC: COSV52973905;