rs7765221

chr6-3108054-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.1576+2003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 151,614 control chromosomes in the GnomAD database, including 66,956 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 0.94 (66956 hom., cov: 26)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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]

LOC107986556 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK1	NM_001354930.2	c.1576+2003A>G		intron_variant		ENST00000259808.9
LOC107986556	XR_001743928.3	n.955-157T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK1	ENST00000259808.9	c.1576+2003A>G		intron_variant		5	NM_001354930.2	P1

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142289 AN: 151496 Hom.: 66898 Cov.: 26

Gnomad AFR AF: 0.981

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.939 AC: 142406 AN: 151614 Hom.: 66956 Cov.: 26 AF XY: 0.942 AC XY: 69741 AN XY: 74032

Gnomad4 AFR AF: 0.981

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.927

Alfa AF: 0.921 Hom.: 34689

Bravo AF: 0.937

Asia WGS AF: 0.945 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.4
Dann	Benign	0.81

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: rs7765221; hg19: chr6-3108288;