10-62222909-A-G

Variant names:

• chr10-62222909-A-G
• rs4147233
• NM_145307.4:c.781+329T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145307.4(RTKN2):​c.781+329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,146 control chromosomes in the GnomAD database, including 43,951 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 0.76 (43951 hom., cov: 32)
• Consequence: RTKN2 NM_145307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 3 publications found

Genes affected

RTKN2 (HGNC:19364): (rhotekin 2) Involved in negative regulation of intrinsic apoptotic signaling pathway; positive regulation of NF-kappaB transcription factor activity; and positive regulation of NIK/NF-kappaB signaling. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTKN2	NM_145307.4	c.781+329T>C		intron_variant	Intron 7 of 11	ENST00000373789.8	NP_660350.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTKN2	ENST00000373789.8	c.781+329T>C		intron_variant	Intron 7 of 11	1	NM_145307.4	ENSP00000362894.3
RTKN2	ENST00000315289.6	c.124+329T>C		intron_variant	Intron 2 of 8	2		ENSP00000325379.2

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115453 AN: 152028 Hom.: 43935 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.759 AC: 115510 AN: 152146 Hom.: 43951 Cov.: 32 AF XY: 0.760 AC XY: 56551 AN XY: 74388

African (AFR) AF: 0.751 AC: 31140 AN: 41482

American (AMR) AF: 0.784 AC: 11976 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2745 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4684 AN: 5182

South Asian (SAS) AF: 0.598 AC: 2883 AN: 4820

European-Finnish (FIN) AF: 0.814 AC: 8627 AN: 10596

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50997 AN: 67996

Other (OTH) AF: 0.753 AC: 1593 AN: 2116

Alfa AF: 0.746 Hom.: 21818

Bravo AF: 0.762

Asia WGS AF: 0.748 AC: 2601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4147233; hg19: chr10-63982668;