19-10566005-T-C

Position:

• chr19-10566005-T-C

Variant summary

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

The NM_023008.5(KRI1):​c.-6A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,511,422 control chromosomes in the GnomAD database, including 404,019 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 0.71 (39551 hom., cov: 36)
  • Exomes 𝑓: 0.73 (364468 hom.)
• Consequence: KRI1 NM_023008.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

KRI1 (HGNC:25769): (KRI1 homolog) This gene overlaps with the gene for cysteine endopeptidase AUT-like 4 in a head-to-tail orientation. [provided by RefSeq, Jul 2008]

KRI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.559416E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRI1	NM_023008.5	c.-6A>G		5_prime_UTR_variant	1/19	ENST00000312962.12	NP_075384.4
KRI1	XM_011528190.3	c.-268A>G		5_prime_UTR_variant	1/18		XP_011526492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRI1	ENST00000312962.12	c.-6A>G		5_prime_UTR_variant	1/19	1	NM_023008.5	ENSP00000320917.9

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108502 AN: 151972 Hom.: 39525 Cov.: 36

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.699

GnomAD3 exomes AF: 0.618 AC: 67360 AN: 109002 Hom.: 22086 AF XY: 0.627 AC XY: 38218 AN XY: 60918

Gnomad AFR exome AF: 0.717

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.587

Gnomad EAS exome AF: 0.320

Gnomad SAS exome AF: 0.587

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.745

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.726 AC: 986962 AN: 1359336 Hom.: 364468 Cov.: 64 AF XY: 0.723 AC XY: 484136 AN XY: 670066

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.758

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.714 AC: 108580 AN: 152086 Hom.: 39551 Cov.: 36 AF XY: 0.705 AC XY: 52384 AN XY: 74338

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.701

Alfa AF: 0.725 Hom.: 54189

Bravo AF: 0.700

TwinsUK AF: 0.754 AC: 2794

ALSPAC AF: 0.758 AC: 2921

ESP6500AA AF: 0.809 AC: 2546

ESP6500EA AF: 0.800 AC: 4779

ExAC AF: 0.471 AC: 12660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.65
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	9.6e-7	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.081
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.010
MPC		0.15
ClinPred		0.0048	T
GERP RS		3.3

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: rs3218222; hg19: chr19-10676681; COSMIC: COSV57263916; COSMIC: COSV57263916;