12-75506616-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007043.7(KRR1):c.394-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (6141 hom., cov: 0)
  • Exomes 𝑓: 0.32 (333 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRR1 NM_007043.7 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0340

Genes affected

KRR1 (HGNC:5176): (KRR1 small subunit processome component homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in chromosome; intercellular bridge; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-75506616-CA-C is Benign according to our data. Variant chr12-75506616-CA-C is described in ClinVar as [Benign]. Clinvar id is 2792650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRR1	NM_007043.7	c.394-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000229214.9
KRR1	XM_047428133.1	c.100-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRR1	ENST00000229214.9	c.394-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007043.7	P1
KRR1	ENST00000438169.6	c.394-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
KRR1	ENST00000550898.1	n.597del		non_coding_transcript_exon_variant	3/3	2
KRR1	ENST00000550023.5	n.410-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 41500 AN: 123226 Hom.: 6150 Cov.: 0

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.332

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.320 AC: 389568 AN: 1218686 Hom.: 333 Cov.: 0 AF XY: 0.318 AC XY: 190051 AN XY: 598232

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.337 AC: 41473 AN: 123206 Hom.: 6141 Cov.: 0 AF XY: 0.337 AC XY: 19784 AN XY: 58626

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.331

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35071517; hg19: chr12-75900396;