chr6-3075319-A-G

Position:

• chr6-3075319-A-G

Variant summary

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

The NM_001354930.2(RIPK1):​c.-60-1445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,958 control chromosomes in the GnomAD database, including 27,723 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 0.60 (27723 hom., cov: 31)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

RIPK1 (HGNC:10019): (receptor interacting serine/threonine kinase 1) This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]

RIPK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK1	NM_001354930.2	c.-60-1445A>G		intron_variant		ENST00000259808.9	NP_001341859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK1	ENST00000259808.9	c.-60-1445A>G		intron_variant		5	NM_001354930.2	ENSP00000259808.3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90664 AN: 151840 Hom.: 27717 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.597 AC: 90696 AN: 151958 Hom.: 27723 Cov.: 31 AF XY: 0.594 AC XY: 44064 AN XY: 74236

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.592

Alfa AF: 0.653 Hom.: 67115

Bravo AF: 0.596

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.88

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: rs2326173; hg19: chr6-3075553;